Professor of Medicine (Cardiovascular Medicine) at the Stanford University Medical Center

Medicine - Cardiovascular Medicine

Bio

Bio

Dr. Fearon graduated from Dartmouth College and received his medical degree from Columbia University College of Physicians and Surgeons, where he was elected into the Alpha Omega Alpha Medical Honor Society. He completed an Internal Medicine residency at Stanford University Medical Center serving an extra year as a Medical Chief Resident. He completed a General Cardiology and Interventional Cardiology fellowship at Stanford, spending his third year as the Chief Cardiology Fellow. He is currently a Professor of Medicine (Cardiology) and Director of Interventional Cardiology at Stanford University. Dr. Fearon is board certified in cardiovascular medicine and interventional cardiology, and he is a fellow of the American College of Cardiology and the Society of Cardiovascular Angiography and Interventions. He was elected to the American Society of Clinical Investigation.Dr. Fearon?s primary area of research interest is in coronary physiology. He was the US principal investigator and senior author of the FAME trial, published in the New England Journal of Medicine and is a co-principal investigator and senior author of the FAME 2 trial, also published in the New England Journal of Medicine. He has presented and published a number of abstracts and peer-reviewed papers in this area, and serves on the editorial board of Circulation, the Journal of the American College of Cardiology, JACC Cardiovascular Interventions, and Circulation: Cardiovascular Interventions. He is the principal investigator on an R01 award from the NIH evaluating cardiac allograft vasculopathy. Dr. Fearon?s clinical activities include not only percutaneous coronary intervention, but also transcatheter aortic valve replacement.

Links

Research & Scholarship

Current Research and Scholarly Interests

Dr. Fearon's general research interest is coronary physiology. In particular, he is investigating invasive methods for evaluating the coronary microcirculation. His research is currently funded by an NIH R01 Award.

Clinical Trials

PCSK9 Inhibition After Heart TransplantationNot Recruiting

The focus of this study is to test the safety and efficacy of the PCSK9 inhibitor, alirocumab
when administered early after heart transplantation (HT).The main objective of this project
is to test the safety and impact on cardiac allograft vasculopathy (CAV) of alirocumab when
given early after HT.

Stanford is currently not accepting patients for this trial.For more information, please contact Study Team, 650-724-2883.

The TAXUS Libert? Post-Approval Study is an FDA-mandated prospective, multi-center study
designed to collect real-world safety and clinical outcomes in approximately 4,200 patients
receiving one or more TAXUS Liberté Paclitaxel-Eluting Stents and prasugrel as part of a dual
antiplatelet therapy (DAPT) drug regimen.
This study will also contribute patient data to an FDA-requested and industry-sponsored
research study that will evaluate the optimal duration of dual antiplatelet therapy (DAPT
Study).

Stanford is currently not accepting patients for this trial.For more information, please contact Yvonne Strawa, (650) 498 - 7028.

This study will assess the differences between Fractional Flow Reserve (FFR) measurements
made by the Navvus catheter and a commercially available pressure guidewire in up to 240
subjects where FFR is clinically indicated. All subjects will receive diagnostic treatment
according to clinical indications and center standard practice.

The purpose of this study is to determine the diagnostic performances of iodine contrast
medium and resting conditions to predict fractional flow reserve (FFR). Reference FFR will be
measured using standard adenosine. We hypothesize that contrast FFR will offer superior
diagnostic agreement compared to resting conditions.

In this multicenter, international study we are evaluating two approaches to determine which
coronary artery narrowings require stent placement in patients with multivessel coronary
artery disease. Patients will be randomized to an angiographic strategy, where only coronary
angiography is used to determine which lesions to stent or to a pressure wire strategy where
fractional flow reserve, an index measured with the pressure wire, will be used to determine
which lesions to stent. The primary outcome will be major adverse cardiac events at 1 year. A
secondary outcome will be cost-effectiveness.

Stanford is currently not accepting patients for this trial.For more information, please contact William Fearon, (650) 725 - 2621.

Cardiac transplantation is the ultimate treatment option for patients with end stage heart
failure.
Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after
transplantation.
Angiotensin converting enzyme inhibitors are used in less than one half of transplant
recipients. Preliminary data suggest that angiotensin converting enzyme inhibitors retard the
atherosclerotic plaque development that is the hallmark of cardiac allograft vasculopathy.
Moreover, this class of drug appears to increase circulating endothelial progenitor cell
number and has anti-inflammatory properties, both of which improve endothelial dysfunction,
the key precursor to the development of cardiac allograft vasculopathy.
The objective of this project is to investigate the role of an angiotensin converting enzyme
inhibitor, ramipril, in preventing the development of cardiac allograft vasculopathy. During
the first month after cardiac transplantation subjects will undergo coronary angiography with
intravascular ultrasound measurements of plaque volume in the left anterior descending
coronary artery. Using a coronary pressure wire, epicardial artery and microvascular
physiology will be assessed. Finally, endothelial function and mediators of endothelial
function, including circulating endothelial progenitor cells, will be measured. Subjects will
then be randomized in a double blind fashion to either ramipril or placebo. After 1 year, the
above assessment will be repeated. The primary endpoint will be the development of cardiac
allograft vasculopathy based on intravascular ultrasound-derived parameters. The second aim
will be to assess the effect of ramipril on endothelial dysfunction early after
transplantation. The final aim is to determine the impact of ramipril on coronary physiology
early after transplantation.

Stanford is currently not accepting patients for this trial.For more information, please contact William Fearon, (650) 725 - 2621.

The purpose of this study is to determine whether Fractional flow reserve (FFR, (coronary
pressure wire-based index for assessing the ischemic potential of a coronary lesion)-guided
percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease
(CAD) will result in similar outcomes to coronary artery bypass graft surgery (CABG).

Abstract

BACKGROUND: Whether the benefit in quality of life (QOL) after percutaneous coronary intervention depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown. This study sought to investigate the relationship between FFR values and improvement in QOL.METHODS: From the FAME 1 and 2 trials (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation), we identified 706 stable patients with coronary artery disease who had at least 1 lesion with an FFR?0.80 that was treated with percutaneous coronary intervention and 185 patients with coronary artery disease who had no lesion with an FFR?0.80 and were treated medically who served as a reference group. QOL was assessed by the European Quality of Life-5 Dimensions index at baseline, 1 month, and 1 year. We assessed the relationship between QOL improvement (defined as the change in European Quality of Life-5 Dimensions index from baseline) and FFR as a continuous value and according to abnormal FFR tertile.RESULTS: QOL improved significantly after percutaneous coronary intervention in each abnormal FFR tertile, whereas it did not change in the reference group. The lowest abnormal FFR subgroup had the greatest improvement in QOL at 1 month ( P<0.001). In mixed-effects models for repeated measures, lower FFR ( P=0.002 for 1 month and 0.049 for 1 year), greater delta FFR ( P=0.021 for 1 month and 0.025 for 1 year), and higher angina class ( P=0.001 for 1 month and <0.001 for 1 year) were associated with the greatest magnitude of QOL improvement at both 1 month and 1 year.CONCLUSIONS: Among patients with stable coronary artery disease, FFR and angina severity predict QOL improvement after percutaneous coronary intervention.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00267774 and NCT01132495.

Abstract

BACKGROUND: Measuring fractional flow reserve (FFR) with a pressure wire remains underutilized due to the invasiveness of guide wire placement and/or the need for a hyperemic stimulus. FFR derived from routine coronary angiography (FFRangio) eliminates both of these requirements and displays FFR values of the entire coronary tree. The FFRangio Accuracy versus Standard FFR (FAST-FFR) study is a prospective, multicenter, international trial with the primary goal of determining the accuracy of FFRangio.METHODS: Coronary angiography was performed in a routine fashion in patients with suspected coronary artery disease. FFR was measured in vessels with coronary lesions of varying severity using a coronary pressure wire and hyperemic stimulus. Based on angiograms of the respective arteries acquired in at least two different projections, on-site operators blinded to FFR then calculated FFRangio using proprietary software. Co-primary endpoints were the sensitivity and specificity of the dichotomously scored FFRangio for predicting pressure wire-derived FFR using a cutoff value of 0.80. The study was powered to meet pre-specified performance goals for sensitivity and specificity.RESULTS: Ten centers in the United States, Europe and Israel enrolled a total of 301 subjects and 319 vessels meeting inclusion/exclusion criteria which were included in the final analysis. The mean FFR was 0.81 and 43% of vessels had an FFR?0.80. The per-vessel sensitivity and specificity were 94% (95% CI 88-97%) and 91% (86-95%), respectively, both of which exceeded the pre-specified performance goals. The diagnostic accuracy of FFRangio was 92% overall and remained high when only considering FFR values between 0.75-0.85 (87%). FFRangio values correlated well with FFR measurements (r=0.80, p<0.001) and the Bland Altman 95% confidence limits were between -0.14 and 0.12. The device success rate for FFRangio was 99%.CONCLUSIONS: FFRangio measured from the coronary angiogram alone has a high sensitivity, specificity and accuracy compared with pressure-wire derived FFR. FFRangio has the promise to substantially increase physiologic coronary lesion assessment in the catheterization laboratory, thereby potentially leading to improved patient outcomes.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT03226262.

Abstract

BACKGROUND: The residual SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (RSS) quantitatively assesses angiographic completeness of revascularization after percutaneous coronary intervention (PCI) and has been shown to be a predictor of events after angiography-guided PCI. In stable patients undergoing functionally complete revascularization with fractional flow reserve (FFR) guidance, RSS did not predict outcome. Whether this is also true in patients with acute coronary syndromes (ACS) is unknown.OBJECTIVES: The purpose of this study was to determine whether the RSS could predict outcomes in patients with ACS.METHODS: From the DANAMI-3-PRIMULTI (Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation), and FAMOUS-NSTEMI (Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes) trials, 547patients presented with ACS and underwent functionally complete revascularization. Major adverse cardiac events (MACE) were defined as the composite endpoint of all-cause death, nonfatal myocardial infarction, and any repeat revascularization. The RSS was based on the recalculation of the SYNTAX score after PCI. We compared differences in 2-year outcome by the RSS subgroups: 0, 1 to<5, 5 to<10,?10 (RSS=0 represents angiographically complete revascularization).RESULTS: The study population consisted of 271 patients with unstable angina/non-ST-segment elevation myocardial infarction and 276 with ST-segment elevation myocardial infarction. The mean RSS was 6.7 ± 5.8. MACE at 2 years occurred in 69patients (12.6%). Patients with and without MACE had similar RSS after PCI (RSS: 7.2 ± 5.5 vs. 6.6 ± 5.9; p=0.23). Kaplan-Meier curve analysis showed a similar incidence of MACE regardless of the RSS subgroups (p=0.54). With and without adjustment of clinical variables, RSS was not a significant predictor of MACE or of each component of MACE.CONCLUSIONS: After complete revascularization of functionally significant stenosis by FFR, the extent of residual angiographic disease is not associated with subsequent ischemic events in patients presenting with ACS. These results suggest that the concept of functionally complete revascularization is applicable even in ACS patients. (Fractional FlowReserve Versus Angiography for Multivessel Evaluation [F.A.M.E.] NCT00267774; Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes [FAMOUS NSTEMI] NCT01764334; Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: TreatmentofCulprit Lesion Only or Complete Revascularization [DANAMI-3-PRIMULTI]; NCT01960933).

Abstract

Background We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. Methods Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ?0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. Results A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. Conclusions In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

Abstract

Previous studies found that percutaneous coronary intervention (PCI) does not improve outcome compared with medical therapy (MT) in patients with stable coronary artery disease, but PCI was guided by angiography alone. FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared PCI guided by fractional flow reserve with best MT in patients with stable coronary artery disease to assess clinical outcomes and cost-effectiveness.A total of 888 patients with stable single-vessel or multivessel coronary artery disease with reduced fractional flow reserve were randomly assigned to PCI plus MT (n=447) or MT alone (n=441). Major adverse cardiac events included death, myocardial infarction, and urgent revascularization. Costs were calculated on the basis of resource use and Medicare reimbursement rates. Changes in quality-adjusted life-years were assessed with utilities determined by the European Quality of Life-5 Dimensions health survey at baseline and over follow-up.Major adverse cardiac events at 3 years were significantly lower in the PCI group compared with the MT group (10.1% versus 22.0%; P<0.001), primarily as a result of a lower rate of urgent revascularization (4.3% versus 17.2%; P<0.001). Death and myocardial infarction were numerically lower in the PCI group (8.3% versus 10.4%; P=0.28). Angina was significantly less severe in the PCI group at all follow-up points to 3 years. Mean initial costs were higher in the PCI group ($9944 versus $4440; P<0.001) but by 3 years were similar between the 2 groups ($16?792 versus $16?737; P=0.94). The incremental cost-effectiveness ratio for PCI compared with MT was $17?300 per quality-adjusted life-year at 2 years and $1600 per quality-adjusted life-year at 3 years. The above findings were robust in sensitivity analyses.PCI of lesions with reduced fractional flow reserve improves long-term outcome and is economically attractive compared with MT alone in patients with stable coronary artery disease.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01132495.

Abstract

Traditionally, invasive coronary physiological assessment has focused on the epicardial coronary artery. More recently, appreciation of the importance of the coronary microvasculature in determining patient outcomes has grown. Several invasive modalities for interrogating microvascular function have been proposed. Angiographic techniques have been limited by their qualitative and subjective nature. Doppler wire-derived coronary flow reserve has been applied in research studies, but its clinical role has been limited by its lack of reproducibility, its lack of a clear normal value, and the fact that it is not specific for the microvasculature but interrogates the entire coronary circulation. The index of microcirculatory resistance-a thermodilution-derived measure of the minimum achievable microvascular resistance-is relatively easy to measure, more reproducible, has a clearer normal value, and is independent of epicardial coronary artery stenosis. The index of microcirculatory resistance has been shown to have prognostic value in patients with ST-segment-elevation myocardial infarction and cardiac allograft vasculopathy after heart transplantation. Emerging data demonstrate its role in evaluating patients with chest pain and nonobstructive coronary artery disease. Increasingly, the index of microcirculatory resistance is used as a reference standard for invasively assessing the microvasculature in clinical trials.

Abstract

Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients.We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort.The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation.In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Abstract

We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy.In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years.The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years.In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

Abstract

We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy.In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years.The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years.In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

Abstract

The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial demonstrated a significant reduction in subsequent coronary revascularization among patients with stable angina and at least 1 coronary lesion with a fractional flow reserve ?0.80 who were randomized to percutaneous coronary intervention (PCI) compared with best medical therapy. The economic and quality-of-life implications of PCI in the setting of an abnormal fractional flow reserve are unknown.We calculated the cost of the index hospitalization based on initial resource use and follow-up costs based on Medicare reimbursements. We assessed patient utility using the EQ-5D health survey with US weights at baseline and 1 month and projected quality-adjusted life-years assuming a linear decline over 3 years in the 1-month utility improvements. We calculated the incremental cost-effectiveness ratio based on cumulative costs over 12 months. Initial costs were significantly higher for PCI in the setting of an abnormal fractional flow reserve than with medical therapy ($9927 versus $3900, P<0.001), but the $6027 difference narrowed over 1-year follow-up to $2883 (P<0.001), mostly because of the cost of subsequent revascularization procedures. Patient utility was improved more at 1 month with PCI than with medical therapy (0.054 versus 0.001 units, P<0.001). The incremental cost-effectiveness ratio of PCI was $36 000 per quality-adjusted life-year, which was robust in bootstrap replications and in sensitivity analyses.PCI of coronary lesions with reduced fractional flow reserve improves outcomes and appears economically attractive compared with best medical therapy among patients with stable angina.

Abstract

BACKGROUND: Most methods for assessing microvascular function are not readily available in the cardiac catheterization laboratory. The aim of this study is to determine whether the Index of Microcirculatory Resistance (IMR), measured at the time of primary percutaneous coronary intervention (PCI) is predictive of death and rehospitalization for heart failure. METHODS AND RESULTS: IMR was measured immediately after primary PCI in 253 patients from 3 institutions using a pressure-temperature sensor wire. The primary endpoint was the rate of death or rehospitalization for heart failure. The prognostic value of IMR was compared to coronary flow reserve, TIMI myocardial perfusion grade and clinical variables. The mean IMR was 40.3 ±32.5. Patients with an IMR>40 had a higher rate of the primary end point at one year compared to patients with an IMR?40 (17.1% vs. 6.6%, p=0.027). During a median follow-up period of 2.8 years, 13.8% suffered the primary end point and 4.3% died. An IMR>40 was associated with an increased risk of death or rehospitalization for heart failure (HR 2.1, p=0.034) and of death alone (HR 3.95, p=0.028). On multivariate analysis, independent predictors of death or rehospitalization for heart failure included IMR>40 (HR 2.2, p=0.026), fractional flow reserve ?0.8 (HR 3.24, p=0.008) and diabetes (HR 4.4, p<0.001). An IMR>40 was the only independent predictor of death alone (HR 4.3, p=0.02). CONCLUSIONS: An elevated IMR at the time of primary PCI predicts poor long term outcomes.

Abstract

The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ?0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event.In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).

Abstract

This study was aimed at investigating whether a fractional flow reserve (FFR)-guided SYNTAX score (SS), termed "functional SYNTAX score" (FSS), would predict clinical outcome better than the classic SS in patients with multivessel coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).The SS is a purely anatomic score based on the coronary angiogram and predicts outcome after PCI in patients with multivessel CAD. FFR-guided PCI improves outcomes by adding functional information to the anatomic information obtained from the angiogram.The SS was prospectively collected in 497 patients enrolled in the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study. FSS was determined by only counting ischemia-producing lesions (FFR ? 0.80). The ability of each score to predict major adverse cardiac events (MACE) at 1 year was compared.The 497 patients were divided into tertiles of risk based on the SS. After determining the FSS for each patient, 32% moved to a lower-risk group as follows. MACE occurred in 9.0%, 11.3%, and 26.7% of patients in the low-, medium-, and high-FSS groups, respectively (p < 0.001). Only FSS and procedure time were independent predictors of 1-year MACE. FSS demonstrated a better predictive accuracy for MACE compared with SS (Harrell's C of FSS, 0.677 vs. SS, 0.630, p = 0.02; integrated discrimination improvement of 1.94%, p < 0.001).Recalculating SS by only incorporating ischemia-producing lesions as determined by FFR decreases the number of higher-risk patients and better discriminates risk for adverse events in patients with multivessel CAD undergoing PCI.

Abstract

The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study demonstrated significantly improved health outcomes at 1 year in patients randomized to multivessel percutaneous coronary intervention guided by fractional flow reserve (FFR) compared with percutaneous coronary intervention guided by angiography alone. The economic impact of routine measurement of FFR in this setting is not known.In this study, 1005 patients were randomly assigned to FFR-guided or angiography-guided percutaneous coronary intervention and followed up for 1 year. A prospective cost-utility analysis comparing costs and quality-adjusted life-years was performed with a time horizon of 1 year. Quality-adjusted life-years were calculated with the use of utilities determined by the EuroQuol 5 dimension health survey with US weights. Direct medical costs included those of the index procedure and hospitalization and costs for major adverse cardiac events during follow-up. Confidence intervals for both quality-adjusted life-years and costs were estimated by the bootstrap percentile method. Major adverse cardiac events at 1 year occurred in 13.2% of those in the FFR-guided arm and 18.3% of those in the angiography-guided arm (P=0.02). Quality-adjusted life-years were slightly greater in the FFR-guided arm (0.853 versus 0.838; P=0.2). Mean overall costs at 1 year were significantly less in the FFR-guided arm ($14 315 versus $16 700; P<0.001). Bootstrap simulation indicated that the FFR-guided strategy was cost-saving in 90.74% and cost-effective at a threshold of US $50 000 per quality-adjusted life-years in 99.96%. Sensitivity analyses demonstrated robust results.Economic evaluation of the FAME study reveals that FFR-guided percutaneous coronary intervention in patients with multivessel coronary disease is one of those rare situations in which a new technology not only improves outcomes but also saves resources. Clinical Trial Registration- URL: http://ClinicalTrials.gov. Unique identifier: NCT00267774.

Abstract

In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention (PCI), coronary angiography is the standard method for guiding the placement of the stent. It is unclear whether routine measurement of fractional flow reserve (FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes.In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year.The mean (+/-SD) number of indicated lesions per patient was 2.7+/-0.9 in the angiography group and 2.8+/-1.0 in the FFR group (P=0.34). The number of stents used per patient was 2.7+/-1.2 and 1.9+/-1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (67 patients) in the FFR group (P=0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P=0.20).Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.)

Abstract

The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging.In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded.The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values 32 U compared with

Abstract

Although its limitations for diagnosing critical coronary artery disease are well described, coronary angiography remains the predominant method for guiding decisions about stent implantation in patients with multivessel coronary artery disease. However, some have suggested that invasive physiologic guidance may improve decision making.The objective of this multicenter, randomized clinical trial is to compare the efficacy of 2 strategies, one based on angiographic guidance to one based on physiologic guidance with fractional flow reserve (FFR), for deciding which coronary lesions to stent in patients with multivessel coronary disease. Eligible patients must have coronary narrowings > 50% diameter stenosis in > or = 2 major epicardial vessels, > or = 2 of which the investigator feels require drug-eluting stent placement. Patients with previous coronary bypass surgery or left main coronary disease are excluded. Based on angiographic evaluation, the investigator notes the lesions that require stenting. The patient is then randomly assigned to either angiographic guidance or FFR guidance. Patients assigned to angiographic guidance undergo stenting as planned. Patients assigned to FFR guidance first have FFR measured in each diseased vessel and only undergo stenting if the FFR is < or = 0.80. The primary end point of the study is a composite of major adverse cardiac events, including death, myocardial infarction, and repeat coronary revascularization, at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, 2-year, and 5-year outcomes.The FAME study will examine for the first time in a large, multicenter, randomized fashion the role of measuring FFR in patients undergoing multivessel percutaneous coronary intervention.

Abstract

A simple, reproducible invasive method for assessing the coronary microcirculation is lacking. A novel index of microcirculatory resistance (IMR) has been shown in animals to correlate with true microvascular resistance and, unlike coronary flow reserve (CFR), to be independent of the epicardial artery. We sought to compare the reproducibility and hemodynamic dependence of IMR with CFR in humans.Using a pressure-temperature sensor-tipped coronary wire, thermodilution-derived CFR and IMR were measured, along with fractional flow reserve (FFR), in 15 coronary arteries (15 patients) under the following hemodynamic conditions: (1) twice at baseline; (2) during right ventricular pacing at 110 bpm; (3) during intravenous infusion of nitroprusside; and (4) during intravenous dobutamine infusion. Mean CFR did not change during baseline measurements or during nitroprusside infusion but decreased during pacing (from 3.1+/-1.1 at baseline to 2.3+/-1.2 during pacing, P<0.05) and during dobutamine infusion (from 3.0+/-1.0 to 1.7+/-0.6 with dobutamine, P<0.0001). By comparison, mean values for IMR and FFR remained similar throughout all hemodynamic conditions. The mean coefficient of variation between 2 baseline measurements was significantly lower for IMR (6.9+/-6.5%) and FFR (1.6+/-1.6%) than for CFR (18.6+/-9.6%; P<0.01). Mean correlation between baseline measurements and each hemodynamic intervention was superior for IMR (r=0.90+/-0.05) and FFR (r=0.86+/-0.12) compared with CFR (r=0.70+/-0.05; P<0.05).Compared with CFR, IMR provides a more reproducible assessment of the microcirculation, which is independent of hemodynamic perturbations. Simultaneous measurement of FFR and IMR may provide a comprehensive and specific assessment of coronary physiology at both epicardial and microvascular levels, respectively.

Abstract

The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements.In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (R(micro app)) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMR(app)]). These apparent resistances were compared with the actual R(micro) and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of R(micro) and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, R(micro app) (0.43+/-0.12 to 0.46+/-0.10 to 0.51+/-0.11 mm Hg/mL per minute) and IMR(app) (14+/-4 to 17+/-7 to 20+/-10 U) increased progressively and significantly with increasing epicardial artery stenosis (P<0.001 for both). With the incorporation of collateral flow, neither R(micro) nor IMR increased as a result of increasing epicardial artery stenosis.After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.

Abstract

A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking.By using a coronary pressure wire and modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9+/-6.5 U to 25.9+/-14.4 U, P=0.002) and TMR (0.51+/-0.14 to 0.79+/-0.32 mm Hg x mL(-1) x min(-1), P=0.0001), as well as the % change in IMR (147+/-66%) and TMR (159+/-105%, P=NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR.Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.

Abstract

OBJECTIVES: To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR).BACKGROUND: The iFR was found to be non-inferior to the gold-standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices.METHODS: Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ?0.80 and ?0.89, respectively).RESULTS: Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n=244 (41.6%), or positive, n=222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR-) in 69 (11.8%) patients and positive discordant (FFR-/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.30[1.68;6.47]), more severe stenosis (OR: 1.77[1.35;2.30]), younger age (OR: 0.93[0.90;0.97]), and slower heart rate (OR: 0.59[0.42;0.75]) were predictors of a negative discordant iFR. Absence of a beta-blocker (OR: 0.41[0.22;0.78]), older age (OR: 1.04[1.00;1.07]), and less severe stenosis (OR: 0.69[0.53;0.89]) were predictors of a positive discordant iFR.CONCLUSIONS: During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR.

Abstract

Dyslipidemia is common in patients undergoing heart transplantation and is associated with the progression of cardiac allograft vasculopathy. Two monoclonal antibodies directed against PCSK9i-evolocumab and alirocumab-are currently available. However, their use, safety and efficacy in the post-transplant setting have not been studied. We present our experience with 6 heart transplant recipients treated with a PCSK9i. A > 70% reduction in LDL-cholesterol was observed after evolocumab therapy. PCSK9 inhibitors are a potentially lipid-lowering therapeutic option for heart transplant patients with suboptimal LDL despite maximal tolerated statin doses.

Abstract

Aims: To assess the effect of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with contemporary drug-eluting stents on the composite of cardiac death or myocardial infarction (MI) vs. medical therapy in patients with stable coronary lesions.Methods and results: We performed a systematic review and meta-analysis of individual patient data (IPD) of the three available randomized trials of contemporary FFR-guided PCI vs. medical therapy for patients with stable coronary lesions: FAME 2 (NCT01132495), DANAMI-3-PRIMULTI (NCT01960933), and Compare-Acute (NCT01399736). FAME 2 enrolled patients with stable coronary artery disease (CAD), while the other two focused on non-culprit lesions in stabilized patients after acute coronary syndrome. A total of 2400 subjects were recruited from 54 sites world-wide with 1056 randomly assigned to FFR-guided PCI and 1344 to medical therapy. The pre-specified primary outcome was a composite of cardiac death or MI. We included data from extended follow-ups for FAME 2 (up to 5.5years follow-up) and DANAMI-3-PRIMULTI (up to 4.7years follow-up). After a median follow-up of 35months (interquartile range 12-60months), a reduction in the composite of cardiac death or MI was observed with FFR-guided PCI as compared with medical therapy (hazard ratio 0.72, 95% confidence interval 0.54-0.96; P=0.02). The difference between groups was driven by MI.Conclusion: In this IPD meta-analysis of the three available randomized controlled trials to date, FFR-guided PCI resulted in a reduction of the composite of cardiac death or MI compared with medical therapy, which was driven by a decreased risk of MI.

Abstract

BACKGROUND: Endothelin-1 (ET-1) has been implicated in the development of post-heart transplantation (HT) cardiac allograft vasculopathy (CAV), but has not been well-studied in humans.METHODS AND RESULTS: In 90 HT patients, plasma ET-1 was measured within 8 weeks of HT (baseline) via a competitive enzyme-linked immunosorbent assay. 3D volumetric intravascular ultrasound of the left anterior descending artery was performed at baseline and at 1 year. Accelerated CAV (lumen volume loss) was defined using the 75th percentile as a cutoff. Patients were followed beyond the first year post-HT for late death or re-transplantation. A receiver operative characteristic curve demonstrated that a baseline ET-1 concentration of 1.75 pg/mL provided the best accuracy for diagnosis of accelerated CAV at 1 year [area under the curve=0.69 (0.57-0.82), p=0.007]. In multivariate logistic regression, a higher baseline ET-1 concentration was independently associated with accelerated CAV [odds ratio (OR)=2.13, 95% confidence interval (CI): 1.15-3.94; p=0.01]; this relationship persisted when ET-1 was dichotomized at 1.75 pg/mL (OR=4.88, 95% CI: 1.69-14.10; p=0.003). Eighteen deaths occurred during a median follow-up period of 3.99 (2.51-9.95) years. Treated as a continuous variable, baseline ET-1 was not associated with late mortality in multivariate Cox regression [hazard ratio (HR)=1.22, 95% CI: 0.72-2.05; p=0.44]. However, ET-1 >1.75 pg/mL conferred a significantly lower cumulative event-free survival on Kaplan-Meier analysis (p=0.047), and was independently associated with late mortality (HR=2.94, 95% CI: 1.12-7.72; p=0.02).CONCLUSIONS: Elevated ET-1 early after HT is an independent predictor of accelerated CAV and late mortality, suggesting that ET-1 has durable prognostic value in the HT arena.

Abstract

OBJECTIVE: Previous studies have suggested that cytokines and growth factors may predict ventricular recovery following aortic valve replacement (AVR). The primary objective of this study was to identify cytokines that predict ventricular recovery following transcatheter AVR (TAVR).METHODS: We prospectively enrolled 121 consecutive patients who underwent TAVR. Standard echocardiographic assessment at baseline, 1-month and 1-year after TAVR included left ventricular (LV) mass index (LVMI) and global longitudinal strain (GLS). Blood samples were obtained at the time of the procedure to measure cytokines using a 63-plex Luminex platform. Partial least squares-discriminant analysis was performed to identify cytokines associated with ventricular remodeling and function at baseline as well as 1?year after TAVR.RESULTS: The mean age was 84?±?9?years, with a majority of male subjects (59%), a mean LVMI of 120.4?±?45.1?g/m2 and LVGLS of -13.0?±?3.2%. On average, LV mass decreased by 8.1% and GLS improved by 20.3% at 1?year following TAVR. Among cytokines assayed, elevated hepatocyte growth factor (HGF) emerged as a common factor significantly associated with worse baseline LVMI and GLS as well as reduced ventricular recovery (p?0.005). Other factors associated with ventricular recovery included a select group of vascular growth factors, inflammatory mediators and tumor necrosis factors, including VEGF-D, ICAM-1, TNFbeta, and IL1beta.CONCLUSION: We identified a network of cytokines, including HGF, that are significantly correlated with baseline LVMI and GLS, and ventricular recovery following TAVR.

Abstract

Cardiac allograft vasculopathy (CAV) is a complex disease that remains a significant cause of morbidity and mortality after orthotopic heart transplantation (OHT). Originating as a result of inflammatory response, the development and progression of CAV is attributed to endothelial dysfunction, cellular infiltration, and a wide-range of genetic and patient factors. The detection of CAV remains a diagnostic challenge, as symptoms can be variable or absent. While coronary angiography remains the initial test of choice for the diagnosis and surveillance of CAV, intravascular imaging (either by ultrasound or optical coherence tomography) and physiologic assessments are useful adjuncts in the cardiac catheterization laboratory. Positron emission tomography, computed tomographic, and magnetic resonance imaging may have a role increasing the time interval between invasive screening tests for prognosis. Medical management should include a statin, vasodilator, and tailored immunosuppressive regimen that maximally decrease allograft rejection and CAV progression while causing minimal side effects. Patients that are less responsive to pharmacotherapy should be considered for invasive management with percutaneous coronary intervention. Although surgical revascularization is a poor option, repeat OHT is the only definitive treatment option but given its morbidity should be reserved for a highly selected patient population.

Abstract

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

Abstract

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

Abstract

There are multiple proposed mechanisms for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). We hypothesized that coronary microvascular dysfunction is common in these patients. In a prospective, observational study, patients undergoing cardiac catheterization with HFpEF [left ventricular (LV) ejection fraction ? 50% and with clinical HF] were compared with similar patients without HFpEF. Patients with ?50% stenosis were excluded, and coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were measured after adenosine administration using a guidewire, with CFR ? 2 and IMR ? 23 being abnormal. Baseline characteristics and CFR and IMR were compared in 30 HFpEF patients and 14 control subjects. Compared with control subjects, HFpEF patients were older (65.4?± 9.6 vs. 55.1?± 3.1 yr, P < 0.01), had higher numbers of comorbidities (4.4?± 1.5 vs. 2.6?± 1.9, P = 0.002), had higher median B-type natriuretic peptide [161 (interquartile range: 75-511) pg/dl vs. 37 (interquartile range: 18.5-111) pg/dl, P < 0.01], and had higher LV end-diastolic pressure (17.8?± 4.2 vs. 8.4?± 4.2, P < 0.01). HFpEF patients had lower CFR (2.55?± 1.60 vs. 3.84?± 1.89, P = 0.024) and higher IMR (26.7?± 10.3 vs. 19.7?± 9.7 units, P = 0.037) than control subjects. Most (71.4%) control subjects had normal coronary physiology, whereas 36.7% of HFpEF patients had both abnormal CFR and IMR and another 36.7% had either abnormal CFR or IMR. In conclusion, this is the first study that has reported invasively determined CFR and IMR in HFpEF patients. We demonstrated the presence of four distinct coronary physiology groups in HFpEF patients. Investigation into the potential mechanisms for these findings is needed. NEW & NOTEWORTHY In this prospective observational study of patients with heart failure with preserved ejection fraction (HFpEF), we found that patients with HFpEF had more abnormalities of coronary flow and resistance than asymptomatic control patients, indicating that coronary microvascular dysfunction may play a role in the HFpEF disease process.

Abstract

Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history.The present analysis included the 607 patients from the FAME 2 trial (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2) in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74±0.16), and DS (by quantitative coronary analysis) varied from 8% to 98% (average 53±15). The primary end point, defined as vessel-oriented clinical end point (VOCE) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent, and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: positive concordance (FFR?0.80; DS?50%), negative concordance (FFR>0.80; DS<50%), positive mismatch (FFR?0.80; DS<50%), and negative mismatch (FFR>0.80; DS?50%).The rate of VOCE was highest in the positive concordance group (log rank: X2=80.96; P=0.001) and lowest in the negative concordance group. The rate of VOCE was higher in the positive mismatch group than in the negative mismatch group (hazard ratio, 0.38; 95% confidence interval, 0.21-0.67; P=0.001). There was no significant difference in VOCE between the positive concordance and positive mismatch groups (FFR?0.80; hazard ratio, 0.77; 95% confidence interval, 0.57-1.09; P=0.149) and no significant difference in rate of VOCE between the negative mismatch and negative concordance groups (FFR>0.80; hazard ratio, 1.89; 95% confidence interval, 0.96-3.74; P=0.067).In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS).URL: https://clinicaltrials.gov. Unique identifier: NCT01132495.

Abstract

While >20% of patients presenting to the cardiac catheterization laboratory with angina have no obstructive coronary artery disease (CAD), a majority (77%) have an occult coronary abnormality (endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB)). There are little data regarding the ability of noninvasive stress testing to identify these occult abnormalities in patients with angina in the absence of obstructive CAD.We retrospectively evaluated 155 patients (76.7% women) with angina and no obstructive CAD who underwent stress echocardiography and/or electrocardiography before angiography. We evaluated Duke treadmill score, heart rate recovery (HRR), metabolic equivalents, and blood pressure response. During angiography, patients underwent invasive testing for endothelial dysfunction (decrease in epicardial coronary artery diameter?>20% after intracoronary acetylcholine), MVD (index of microcirculatory resistance ?25), and intravascular ultrasound for the presence of an MB.Stress echocardiography and electrocardiography were positive in 58 (43.6%) and 57 (36.7%) patients, respectively. Endothelial dysfunction was present in 96 (64%), MVD in 32 (20.6%), and an MB in 83 (53.9%). On multivariable logistic regression, stress echo was not associated with any abnormality, while stress ECG was associated with endothelial dysfunction. An abnormal HRR was associated with endothelial dysfunction and MVD, but not an MB.Conventional stress testing is insufficient for identifying occult coronary abnormalities that are frequently present in patients with angina in the absence of obstructive CAD. A normal stress test does not rule out a non-obstructive coronary etiology of angina, nor does it negate the need for comprehensive invasive testing.

Abstract

Invasively assessed coronary microvascular resistance early after heart transplantation predicts worse long-term outcome; however, little is known about the relationship between microvascular resistance, left ventricular function and outcomes in this setting.A total of 100 cardiac transplant recipients had fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) measured in the left anterior descending artery and echocardiographic assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at 1?year after heart transplantation. The primary endpoint was the composite of death and retransplantation occurring beyond the first post-operative year.The mean FFR, IMR, LVEF, and GLS values at 1?year were 0.87?±?0.06, 21.3?±?17.3, 60.4?±?5.4%, and 14.2?±?2.4%, respectively. FFR and IMR had no significant correlation with LVEF and GLS. During a mean follow-up of 6.7?±?4.2?years, the primary endpoint occurred in 24 patients (24.0%). By ROC curve analysis, IMR?=?19.3 and GLS?=?13.3% were the best cutoff values for predicting death or retransplantation. Cumulative event-free survival was significantly lower in patients with higher IMR (log-rank p?=?0.02) and lower GLS (log-rank p?0.001). Cumulative event-free survival can be further stratified by the combination of IMR and GLS (long-rank p?0.001). By multivariable Cox proportional hazards model, higher IMR and lower GLS were independently associated with long-term death or retransplantation (elevated IMR, hazard ratio?=?2.50, p?=?0.04 and reduced GLS, hazard ratio?=?3.79, p?=?0.003, respectively).Invasively assessed IMR does not correlate with GLS at 1?year after heart transplantation. IMR and GLS determined at 1?year may be used as independent predictors of late death or retransplantation.

Abstract

Most immunosuppressive drugs provide targeted immunosuppression by selective inhibition of lymphocyte activation and proliferation. This study evaluated whether a change in the lymphocyte to neutrophil ratio (LNR) is related to acute rejection.In 74 cardiac transplant recipients peripheral blood lymphocyte and neutrophil counts were measured soon after (baseline) and three, six, and 12months after heart transplantation. The primary endpoint was the incidence of acute rejection.Significant acute rejection after heart transplantation occurred in 20 patients (27%) during a median follow-up of 49.4 [IQR 37.4-61.1] months. LNR significantly increased over time (0.1149±0.1354 at baseline, 0.2330±0.2266 at 3months, 0.2961±0.2849 at 6months, and 0.3521±0.2383 at 12months; P<0.001), especially during the first 3months in the group without acute rejection. The area under the curve of the change in LNR during the first three months (?LNR) for acute rejection was 0.565 (95% CI 0.420 to 0.710, P=0.380) on ROC curve analysis. The best cutoff value of ? LNR to differentiate those with and without acute rejection was ?0.046 by ROC curve analysis. Kaplan-Meier analysis revealed that the low ?LNR group (?0.046) had a significantly higher rate of acute rejection than the high ?LNR group (>0.046) (37.5% vs. 19.0%, log-rank: P=0.0358). The low ?LNR for the first 3months was an independent predictor of clinically significant acute rejection after adjusting for cytomegalovirus donor seropositive and recipient seronegative.The results of this study suggest that ?LNR over the first 3months after heart transplantation is a strong and independent predictor of acute rejection after heart transplantation. ?LNR can be used as an early biomarker for predicting of acute rejection after heart transplantation.

Abstract

BACKGROUND: Measurement of fractional flow reserve (FFR) to guide coronary revascularization lags despite robust supportive data, partly because of the handling characteristics of traditional coronary pressure wires. An optical pressure-monitoring microcatheter, which can be advanced over a traditional coronary guidewire, facilitates FFR assessment but may underestimate pressure wire-derived FFR.METHODS AND RESULTS: In this prospective, multicenter trial, 169 patients underwent FFR assessment with a pressure wire alone and with a pressure microcatheter over the pressure wire. An independent core laboratory performed quantitative coronary angiography and evaluated all pressure tracings. The primary end point was the bias or difference between the microcatheter FFR and the pressure wire FFR, as assessed by Bland-Altman analysis. The mean difference between the microcatheter and the pressure wire-derived FFR values was -0.022 (95% confidence interval, -0.029 to -0.015). On multivariable analysis, reference vessel diameter (P=0.027) and lesion length (P=0.044) were independent predictors of bias between the 2 FFR measurements. When the microcatheter FFR was added to this model, it was the only independent predictor of bias (P<0.001). The mean FFR value from the microcatheter was significantly lower than from the pressure wire (0.81 versus 0.83; P<0.001). In 3% of cases (95% confidence interval, 1.3%-6.7%), there was clinically meaningful diagnostic discordance, with the FFR from the pressure wire >0.80 and that from the microcatheter <0.75. These findings were similar when including all 210 patients with site-reported paired FFR data.CONCLUSIONS: An optical, pressure-monitoring microcatheter measures lower FFR compared with a pressure wire, but the diagnostic impact appears to be minimal in most cases.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02577484.

Abstract

Valvulo-arterial impedance (Zva) has been shown to predict worse outcome in medically managed aortic stenosis (AS) patients. We aimed to investigate the association between Zva and left ventricular (LV) adaptation and to explore the predictive value of Zva for cardiac functional recovery and outcome after transcatheter aortic valve replacement (TAVR). We prospectively enrolled 128 patients with AS who underwent TAVR. Zva was calculated as: (systolic blood pressure?+?mean transaortic gradient)/stroke volume index). Echocardiographic assessment occurred at baseline, 1-month and 1-year after TAVR. The primary endpoints were to investigate associations between Zva and global longitudinal strain (GLS) at baseline as well as GLS change after TAVR. The secondary was to compare all-cause mortality after TAVR between patients with pre-defined Zva (=5 mmHg m(2)/ml), stroke volume index (=35 ml/m(2)), and GLS (=-15%) cutoffs. The mean GLS was reduced (-13.0?±?3.2%). The mean Zva was 5.2?±?1.6 mmHg*m(2)/ml with 55% of values ?5.0 mmHg*m(2)/ml, considered to be abnormally high. Higher Zva correlated with worse GLS (r?=?-0.33, p?0.001). After TAVR, Zva decreased significantly (5.1?±?1.6 vs. 4.5?±?1.6 mmHg*m(2)/ml, p?=?0.001). A reduction of Zva at 1-month was associated with GLS improvement at 1-month (r?=?-0.31, p?=?0.001) and at 1-year (r?=?-0.36 and p?=?0.001). By Kaplan-Meier analysis, patients with higher Zva at baseline had higher mortality (Log-rank p?=?0.046), while stroke volume index and GLS did not differentiate outcome (Log-rank p?=?0.09 and 0.25, respectively). As a conclusion, Zva is correlated with GLS in AS as well as GLS improvement after TAVR. Furthermore, a high baseline Zva may have an additional impact to traditional parameters on predicting worse mortality after TAVR.

Abstract

Transcatheter aortic valve replacement (TAVR) has developed into an important alternative to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis (AS). Adjuvant antithrombotic therapies are commonly used during and after TAVR to decrease the risk of valve thrombosis and thromboembolic cerebrovascular events (CVEs) but consequently increase the risk of bleeding. This article reviews the past and current clinical data regarding adjuvant antithrombotic therapies in TAVR.Cerebrovascular and bleeding events during and after TAVR are associated with substantial morbidity and mortality. Bivalirudin, a direct thrombin inhibitor, has been shown to be safe alternative to unfractionated heparin (UFH) as procedural anticoagulation during TAVR; however, sparse evidence exists to guide use of antiplatelet and anticoagulant therapies in patients after TAVR. Multiple studies comparing different antithrombotic regimens in the post-TAVR setting are currently underway. Current guidelines recommend intra-procedural anticoagulation with UFH for during TAVR and with dual antiplatelet therapy (DAPT) after TAVR. There is a need to better understand the role of adjuvant antithrombotic therapies in TAVR. The results of ongoing studies are needed to develop evidence-based guidance for the use of adjuvant antithrombotic therapies after TAVR.

Abstract

Adenosine-free coronary pressure wire metrics have been proposed to test the functional significance of coronary artery lesions, but it is unexplored whether their diagnostic performance might be altered in patients with diabetes.We performed a post-hoc analysis of the CONTRAST study, which prospectively enrolled an international cohort of patients undergoing routine fractional flow reserve (FFR) assessment for standard indications. Paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, contrast-based FFR, and FFR) were made. A central core laboratory analyzed blinded pressure tracings in a standardized fashion.Of 763 subjects enrolled at 12 international centers, 219 (29%) had diabetes. The two groups were well-balanced for age, clinical presentation (stable or unstable), coronary vessel studied, volume and type of intracoronary contrast, and volume of intracoronary adenosine. A binary threshold of cFFR ? 0.83 produced an accuracy superior to both Pd/Pa and iFR when compared with FFR ? 0.80 in the absence of significant interaction with diabetes status; indeed, accuracy in subgroups of patients with or without diabetes was similar for cFFR (86.7 vs 85.4% respectively; p = 0.76), iFR (84.2 vs 80.0%, p = 0.29) and Pd/Pa (81.3 vs 78.9%, p = 0.55). There was no significant heterogeneity between patients with or without diabetes in terms of sensitivity and specificity of all metrics. The area under the receiver operating characteristic (ROC) curve was largest for cFFR compared with Pd/Pa and iFR which were equivalent (cFFR 0.961 and 0.928; Pd/Pa 0.916 and 0.870; iFR 0.911 and 0.861 in diabetic and non-diabetic patients respectively).cFFR provides superior diagnostic performance compared with Pd/Pa or iFR for predicting FFR irrespective of diabetes (clinicaltrials.gov identifier NCT02184117).

Abstract

Difficulty directly visualizing the coronary microvasculature as opposed to the epicardial coronary artery makes its assessment challenging. The goal of this study is to measure the index of microcirculatory resistance (IMR) in all 3 major coronary vessels to identify the clinical and angiographic predictors of an abnormal IMR.Ninety-three patients who underwent coronary physiological assessment in all 3 major coronary vessels were prospectively enrolled (59.8±9.4 years with 77.4% men). IMR was corrected using Yong's formula and coronary microvascular dysfunction (CMD) was defined using vessel-specific cutoffs. A global IMR was calculated as the sum of the IMR in all 3 major epicardial vessels. Angiographic epicardial disease severity was assessed with vessel-specific and overall SYNTAX score. Median IMR and fractional flow reserve was 17.2 (Q1-Q3: 13.3-22.9) and 0.92 (0.85-0.97). The majority of patients (59.1%) had no CMD, 23.7% had 1-vessel CMD, 14.0% had 2-vessel CMD, and 3.2% had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery 28.0%, left circumflex artery 19.4%, and right coronary artery 23.7%; P=0.39). Fractional flow reserve had a weak, positive correlation with IMR (?=0.16; P<0.01). The SYNTAX score had no significant correlation with IMR, both at a patient level (?=-0.002; P=0.99) and a vessel-specific level (?=-0.06; P=0.36). By multivariable ordinal logistic regression analysis, no variable was left as an independent predictor of an abnormal IMR.Clinical factors and epicardial coronary disease severity are not predictors of the extent of CMD.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01621438.

Abstract

Recent data suggest that circulating biomarkers may predict outcome in patients undergoing transcatheter aortic valve replacement (TAVR). We examined the association between inflammatory, myocardial, and renal biomarkers and their role in ventricular recovery and outcome after TAVR.A total of 112 subjects undergoing TAVR were included in the prospective registry. Plasma levels of B-type natriuretic peptide, hs-TnI (high-sensitivity troponin I), CRP (C-reactive protein), GDF-15 (growth differentiation factor 15), GAL-3 (galectin-3), and Cys-C (cystatin-C) were assessed before TAVR and in 100 sex-matched healthy controls. Among echocardiographic parameters, we measured global longitudinal strain, indexed left ventricular mass, and indexed left atrial volume. The TAVR group included 59% male, with an average age of 84 years, and 1-year mortality of 18%. Among biomarkers, we found GDF-15 and CRP to be strongly associated with all-cause mortality (P<0.001). Inclusion of GDF-15 and CRP to the Society of Thoracic Surgeons score significantly improved C index (0.65-0.79; P<0.05) and provided a category-free net reclassification improvement of 106% at 2 years (P=0.01). Among survivors, functional recovery in global longitudinal strain (>15% improvement) and indexed left ventricular mass (>20% decrease) at 1 year occurred in 48% and 22%, respectively. On multivariate logistic regression, lower baseline GDF-15 was associated with improved global longitudinal strain at 1 year (hazard ratio=0.29; P<0.001). Furthermore, improvement in global longitudinal strain at 1 month correlated with lower overall mortality (hazard ratio=0.45; P=0.03).Elevated GDF-15 correlates with lack of reverse remodeling and increased mortality after TAVR and improves risk prediction of mortality when added to the Society of Thoracic Surgeons score.

Abstract

The aim of this study was to determine the value of the ratio of the percentage of circulating regulatory cluster of differentiation 4 T cells (%Tregs) to the percentage of endothelial progenitor cells (%EPCs; Treg/EPC ratio) for predicting clinically significant acute rejection.Peripheral blood %Tregs and %EPCs were quantified in 91 cardiac transplant recipients using flow cytometry at a mean of 42 ± 13 days after transplant. The primary end point was clinically significant acute rejection, defined as an event that led to an acute augmentation of immunosuppression in conjunction with an International Society for Heart and Lung Transplantation grade ? 2R in a right ventricular endomyocardial biopsy specimen or non-cellular rejection (specimen-negative rejection) with hemodynamic compromise (decrease in left ventricular ejection fraction by > 25%).Significant rejection occurred in 27 recipients (29.7%) during a median of 49.4 months (interquartile range, 37.0-62.0 months). The mean %Tregs and %EPCs were not significantly different between those with and without an episode of significant rejection, but the mean Treg/EPC ratio was significantly lower in recipients with significant rejection (44.9 vs 106.7, p = 0.001). Receiver operating characteristic curve analysis showed an area under the curve value for significant rejection for a Treg/EPC ratio of 0.712. The best cutoff value of the Treg/EPC ratio that distinguished between those with or without significant rejection was ? 18 by receiver operating characteristic curve analysis. Kaplan-Meier analysis revealed that patients with a Treg/EPC ratio of ? 18 had a significantly higher rate of rejection than those with a Treg/EPC ratio > 18 (61.5% vs 16.9%, log-rank p < 0.0001). A low Treg/EPC ratio was an independent predictor of significant rejection.A low Treg/EPC ratio measured soon after heart transplantation is an independent predictor of acute rejection. The Treg/EPC ratio has potential as an early biomarker after heart transplantation for predicting acute rejection.

Abstract

This study investigated to define graft dysfunction and to determine its incremental association with long-term outcome after heart transplantation (HT).Although graft failure is an established cause of late mortality after HT, few studies have analyzed the prognostic value of graft dysfunction at 1- and 5-year follow-up of HT.Patients who underwent HT and completed their first annual evaluation with right heart catheterization and echocardiography at Stanford University between January 1999 and December 2011 were included in the study. Hierarchical clustering was used to identify modules to capture independent features of graft dysfunction at 1 year. The primary endpoint for analysis consisted of the composite of cardiovascular mortality, re-transplantation, or heart failure hospitalization within 5 years of HT. The study further explored whether changes in graft dysfunction between 1 and 5 years were associated with 10-year all-cause mortality.A total of 215 HT recipients were included in the study. Using hierarchical clustering, 3 functional modules were identified; among them, left ventricular global longitudinal strain (LVGLS), stroke volume index, and right atrial pressure (RAP) or pulmonary capillary wedge pressure (PCWP) captured key features of graft function. Graft dysfunction based on pre defined LVGLS in absolute value <14%, stroke volume index <35 ml/m2, RAP >10 mm Hg, or PCWP >15 mm Hg were present in 41%, 36%, and 27%, respectively. The primary endpoint at 5 years occurred in 52 patients (24%), whereas 10-year all-cause mortality occurred in 30 (27%) of 110 patients alive at 5 years. On multivariate analysis, RAP (standardized hazard ratio: 1.63), LVGLS (standardized hazard ratio: 1.39), and a history of hemodynamically compromising rejection within 1 year (hazard ratio: 2.18) were independent predictors of 5-year outcome. RAP at 5 years, as well as change in RAP from 1 to 5 years, was predictive of 10-year all-cause mortality.RAP and LVGLS at the first annual evaluation provide complementary prognostic information in predicting 5-year outcome after HT.

Abstract

Contrast fractional flow reserve (cFFR) is a method for assessing functional significance of coronary stenoses, which is more accurate than resting indices and does not require adenosine. However, contrast media volume and osmolality may affect the degree of hyperemia and therefore diagnostic performance.cFFR, instantaneous wave-free ratio, distal pressure/aortic pressure at rest, and FFR were measured in 763 patients from 12 centers. We compared the diagnostic performance of cFFR between patients receiving low or iso-osmolality contrast (n=574 versus 189) and low or high contrast volume (n=341 versus 422) using FFR?0.80 as a reference standard. The sensitivity, specificity, and overall accuracy of cFFR for the low versus iso-osmolality groups were 73%, 93%, and 85% versus 87%, 90%, and 89%, and for the low versus high contrast volume groups were 69%, 99%, and 83% versus 82%, 93%, and 88%. By receiver operating characteristics (ROC) analysis, cFFR provided better diagnostic performance than resting indices regardless of contrast osmolality and volume (P<0.001 for all groups). There was no significant difference between the area under the curve of cFFR in the low- and iso-osmolality groups (0.938 versus 0.957; P=0.40) and in the low- and high-volume groups (0.939 versus 0.949; P=0.61). Multivariable logistic regression analysis showed that neither contrast osmolality nor volume affected the overall accuracy of cFFR; however, both affected the sensitivity and specificity.The overall accuracy of cFFR is greater than instantaneous wave-free ratio and distal pressure/aortic pressure and not significantly affected by contrast volume and osmolality. However, contrast volume and osmolality do affect the sensitivity and specificity of cFFR.URL: https://www.clinicaltrials.gov. Unique identifier: NCT02184117.

Abstract

This work compares the diagnostic performance of adenosine-free coronary pressure wire indices based on lesion location.Several adenosine-free coronary pressure wire indices have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that lesion location and the mass of perfused myocardium may affect diagnostic performance.A total of 763 patients were prospectively enrolled from 12 institutions. Fractional flow reserve (FFR) and contrast-based FFR (cFFR) were obtained during adenosine-induced maximal hyperemia and contrast-induced submaximal hyperemia respectively, whereas the instantaneous wave-free ratio (iFR) and distal pressure/aortic pressure (Pd/Pa) were obtained at rest. Using an FFR of ?0.80 as a reference standard, the diagnostic accuracy of each index was compared based on lesion location (left main or proximal left anterior descending artery [LM/pLAD] compared with other lesion locations).The median FFR, cFFR, iFR, and Pd/Pa were 0.81 (interquartile range [IQR]: 0.74 to 0.87), 0.86 (IQR: 0.79 to 0.91), 0.90 (IQR: 0.85 to 0.94), and 0.92 (IQR: 0.88 to 0.95), respectively. The cFFR, iFR, and Pd/Pa were less accurate in LM/pLAD compared with other lesion locations (cFFR: 80.3% vs. 87.8%; iFR: 73.3% vs. 81.8%; Pd/Pa: 71.4% vs. 81.1%, respectively). By receiver-operating characteristics curve analysis, cFFR provided better diagnostic accuracy than resting indices regardless of lesion location (p ?0.0001 vs. iFR and Pd/Pa for both groups).The cFFR, iFR, and Pd/Pa are less accurate in LM/pLAD compared with other lesion locations, likely related to the larger amount of myocardium supplied by LM/pLAD. Nevertheless, cFFR provides the best diagnostic accuracy among the adenosine-free indices, regardless of lesion location.

Abstract

In patients with coronary artery disease, clinical outcome depends on the extent of reversible myocardial ischemia. Whether the outcome also depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown.This study sought to investigate the relationship between FFR values and vessel-related clinical outcome.We prospectively studied major adverse cardiovascular events (MACE) at 2 years in 607 patients in whom all stenoses were assessed by FFR and who were treated with medical therapy alone. The relationship between FFR and 2-year MACE was assessed as a continuous function. Logistic and Cox proportional hazards regression models were used to calculate the average decrease in the risk of MACE per 0.05-U increase in FFR.MACE occurred in 272 (26.5%) of 1,029 lesions. Target lesions with diameter stenosis ?70% were more often present in the MACE group (p < 0.01). Median FFR was significantly lower in the MACE group versus the non-MACE group (0.68 [interquartile range: 0.54 to 0.77] vs. 0.80 [interquartile range: 0.70 to 0.88]; p < 0.01). The cumulative incidence of MACE significantly increased with increasing FFR quartiles. An average decrease in MACE per 0.05-unit increase in FFR was statistically significant even after adjustment for all clinical and angiographic features (odds ratio: 0.81; 95% confidence interval: 0.76 to 0.86]). The strongest increase in MACE occurred for FFR values between 0.80 and 0.60. In multivariable Cox regression analysis, FFR was significantly associated with MACE up to 2 years (hazard ratio: 0.87; 95% confidence interval: 0.83 to 0.91]).In patients with stable coronary disease, stenosis severity as assessed by FFR is a major and independent predictor of lesion-related outcome. (FAME II - Fractional Flow Reserve [FFR] Guided Percutaneous Coronary Intervention [PCI] Plus Optimal Medical Treatment [OMT] Verses OMT; NCT01132495).

Abstract

Although cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events.This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation.In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation.At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality.ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

Abstract

The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD).Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients <65 years old were compared with those of 87 patients ?65 years old. There was no difference in lesion location, diameter stenosis, minimum lumen area, plaque burden, or lesion length between the 2 age groups. Elderly patients had higher FFR (0.81±0.06 vs. 0.79±0.06, P=0.004) and lower ?FFR, defined as the difference between resting Pd/Pa and FFR (0.13±0.05 vs. 0.15±0.05, P=0.014). Age, along with the location and degree of stenosis, was independently associated with FFR and ?FFR (?=0.162, P=0.008; ?=-0.131, P=0.043, respectively).Elderly patients with intermediate CAD are more likely to have higher FFR and lower ?FFR, despite a similar degree of epicardial stenosis, compared with younger patients. (Circ J 2016; 80: 1583-1589).

Abstract

This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested.Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ?2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ?3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ? 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment.During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036).The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.

Abstract

-The aim of this study is to determine the prognostic value of invasively assessing coronary physiology early after heart transplantation.-Seventy-four cardiac transplant recipients had fractional flow reserve (FFR), coronary flow reserve (CFR), the index of microcirculatory resistance (IMR) and intravascular ultrasound (IVUS) performed down the left anterior descending coronary artery soon after (baseline) and 1 year after heart transplantation. The primary endpoint was the cumulative survival free of death or retransplantation at a mean follow-up of 4.5±3.5 years. The cumulative event-free survival was significantly lower in patients with an FFR<0.90 at baseline (42 vs 79%, p=0.01) or an IMR?20 measured one year after heart transplantation (39 vs. 69%, p=0.03). Patients in whom IMR decreased or did not change from baseline to 1 year had higher event-free survival compared to those patients with an increase in IMR (66 vs. 36%, p=0.03). FFR<0.90 at baseline (hazards ratio [HR] 0.13, 95% confidence interval [CI] 0.02-0.81, p=0.03), IMR ?20 at 1 year (HR 3.93, 95% CI 1.08-14.27, p=0.04) and rejection during the first year (HR 6.00, 95% CI 1.56-23.09, p=0.009) were independent predictors of death/retransplantation, while IVUS parameters were not.-Invasive measures of coronary physiology (FFR and IMR) determined early after heart transplantation are significant predictors of late death or retransplantation.

Abstract

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) significantly improves outcomes compared with angio-guided PCI in patients with multivessel coronary artery disease. However, there is a theoretical concern that in patients with reduced left ventricular ejection fraction (EF) FFR may be less accurate and FFR-guided PCI less beneficial.From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial database, we compared FFR values between patients with reduced EF (both ?40%, n=90 and ?50%, n=252) and preserved EF (>40%, n=825 and >50%, n=663) according to the angiographic stenosis severity. We also compared differences in 1year outcomes between FFR- vs. angio-guided PCI in patients with reduced and preserved EF.Both groups had similar FFR values in lesions with 50-70% stenosis (p=0.49) and with 71-90% stenosis (p=0.89). The reduced EF group had a higher mean FFR compared to the preserved EF group across lesions with 91-99% stenosis (0.55 vs. 0.50, p=0.02), although the vast majority of FFR values remained ?0.80. There was a similar reduction in the composite end point of death, nonfatal myocardial infarction, and repeat revascularization with FFR-guided compared to angio-guided PCI for both the reduced (14.5% vs. 19.0%, relative risk=0.76, p=0.34) and the preserved EF group (13.8 vs. 17.0%, relative risk=0.81, p=0.25). The results were similar with an EF cutoff of 40%.Reduced EF has no influence on the FFR value unless the stenosis is very tight, in which case a theoretically explainable, but clinically irrelevant overestimation might occur. As a result, FFR-guided PCI remains beneficial regardless of EF.

Abstract

This study sought to evaluate the impact of atrial fibrillation (AF) on clinical outcomes in patients undergoing transcatheter aortic valve replacement.Data were evaluated in 1879 patients with baseline and discharge ECGs who underwent transcatheter aortic valve replacement in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. A total of 1262 patients manifested sinus rhythm (SR) at baseline/SR at discharge, 113 SR baseline/AF discharge, and 470 AF baseline/AF discharge. Patients who converted from SR to AF by discharge had the highest rates of all-cause mortality at 30 days (P<0.0001 across all groups; 14.2% SR/AF versus 2.6% SR/SR; adjusted hazard ratio [HR]=3.41; P=0.0002) and over 2-fold difference at 1 year (P<0.0001 across all groups; 35.7% SR/AF versus 15.8% SR/SR; adjusted HR=2.14; P<0.0001). The presence of AF on baseline or discharge ECG was a predictor of 1-year mortality (adjusted HR=2.14 for SR/AF group and HR=1.88 for AF/AF groups; P<0.0001 for both groups versus SR/SR). For patients discharged in AF, those with lower ventricular response (ie, <90 bpm) experienced less 1-year all-cause mortality (HR=0.74; P=0.04).After transcatheter aortic valve replacement, the presence of AF at discharge, and particularly, the conversion to AF by discharge and higher ventricular response are associated with increased mortality. These data underscore the deleterious impact of AF, as well as the need for targeted interventions to improve clinical outcomes, in patients undergoing transcatheter aortic valve replacement.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Abstract

This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation.CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries.In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [?vessel volume/?intimal volume <0].After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015).Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

Abstract

This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation.CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries.In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [?vessel volume/?intimal volume <0].After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015).Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

Abstract

In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up.The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ? 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774.After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001).The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients.St Jude Medical, Friends of the Heart Foundation, and Medtronic.

Abstract

Guidelines recommend coronary artery bypass graft (CABG) surgery over percutaneous coronary intervention (PCI) for the treatment of 3-vessel coronary artery disease (3-VD). The inferior results of PCI demonstrated by previous large randomized trials comparing PCI and CABG might be explained by the use of suboptimal stent technology and by the lack of fractional flow reserve (FFR) guidance of PCI.The objective of this investigator-initiated, multicenter, randomized clinical trial is to investigate whether FFR-guided PCI with new-generation stents is noninferior to CABG in patients with 3-VD, not including the left main coronary artery. Eligible patients must have ?50% coronary stenoses in all 3 major epicardial vessels or major side branches. Patients with a nondominant right coronary artery may be included only if the left anterior descending artery and left circumflex have ?50% stenoses. Consecutive patients who meet all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to either CABG or FFR-guided PCI. Coronary artery bypass graft will be performed based on the angiogram as per clinical routine. Patients assigned to FFR-guided PCI will have FFR measured in each diseased vessel and only undergo stenting if the FFR is ?0.80. The primary end point of the study is a composite of major adverse cardiac and cerebrovascular events, including death, myocardial infarction, repeat coronary revascularization, and stroke at 1 year. Key secondary end point will be a composite of death, myocardial infarction, and stroke at 3-year follow-up. Other secondary end points include the individual adverse events, cost-effectiveness, and quality of life at 2-year, 3-year, with up to 5-year follow-up.The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-VD.

Abstract

Temporary percutaneous mechanical circulatory support (MCS) devices were introduced in the 1960s and have developed into a diverse portfolio of options currently available for left, right, and biventricular support. Patients undergoing high-risk percutaneous coronary interventions (PCI), patients with acute myocardial infarction (AMI), and patients with cardiogenic shock in particular may benefit from these options. In this review, we will discuss the currently available devices and the evidence supporting their use in cardiogenic shock.

Abstract

Stress-induced cardiomyopathy (SCM) is a reversible cardiomyopathy observed in patients without significant coronary disease. The aim of this study was to assess the incidence and clinical significance of right ventricular (RV) involvement in SCM.We retrospectively analyzed echocardiograms from 40 consecutive patients who presented with SCM at Stanford University Medical Center from September 2000 to November 2010. The primary end point was overall mortality. RV involvement was observed in 20 patients (50%; global RV hypokinesia in 15 patients and focal RV apical akinesia in 5 patients). The independent correlates of RV involvement were older age (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.7two, P = .01) and LVEF (per 10% decrease: OR 3.60, CI 1.77-7.32; P = .02). At a mean follow-up of 44 ± 32 months, 12 patients (30%) died (in-hospital death in 3 patients). At multivariate analysis, the presence of an RV fractional area change <35% emerged as an independent predictor of death (OR 3.6, CI 1.06-12.41; P = .04).RV involvement is a common finding in SCM, and may present as either global or focal RV apical involvement. Both older age and lower LVEF are associated with a higher risk of RV involvement, which appears to be a major predictor of death.

Abstract

More than 20% of patients presenting to the cardiac catheterization laboratory with angina have no angiographic evidence of coronary artery disease. Despite a "normal" angiogram, these patients often have persistent symptoms, recurrent hospitalizations, a poor functional status, and adverse cardiovascular outcomes, without a clear diagnosis.In 139 patients with angina in the absence of obstructive coronary artery disease (no diameter stenosis >50%), endothelial function was assessed; the index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve were measured; and intravascular ultrasound was performed. There were no complications. The average age was 54.0±11.4 years, and 107 (77%) were women. All patients had at least some evidence of atherosclerosis based on an intravascular ultrasound examination of the left anterior descending artery. Endothelial dysfunction (a decrease in luminal diameter of >20% after intracoronary acetylcholine) was present in 61 patients (44%). Microvascular impairment (an index of microcirculatory resistance ?25) was present in 29 patients (21%). Seven patients (5%) had a fractional flow reserve ?0.80. A myocardial bridge was present in 70 patients (58%). Overall, only 32 patients (23%) had no coronary explanation for their angina, with normal endothelial function, normal coronary physiological assessment, and no myocardial bridging.The majority of patients with angina in the absence of obstructive coronary artery disease have occult coronary abnormalities. A comprehensive invasive assessment of these patients at the time of coronary angiography can be performed safely and provides important diagnostic information that may affect treatment and outcomes.

Abstract

The aims of this study were to evaluate the effect of left ventricular (LV) dysfunction on clinical outcomes after transcatheter aortic valve replacement (TAVR) and standard therapy for severe aortic stenosis (AS) and to assess LV ejection fraction (LVEF) recovery and its impact on subsequent clinical outcomes.Cohort B of the Placement of AoRtic TraNscathetER Valves trial randomised 342 inoperable patients with severe AS to TAVR or standard therapy. We defined LV dysfunction as an LVEF <50% and LVEF improvement as an absolute increase in LVEF ?10% at 30?days.Baseline LV dysfunction did not affect survival after TAVR but was associated with increased cardiac mortality at 1 year with standard therapy (59.3% vs 45.8% with normal LVEF; HR=1.71 (95% CI 1.08 to 2.71); p=0.02). In those with LV dysfunction, LVEF improvement occurred in 48.7% and 30.4% of TAVR and standard therapy patients, respectively (p=0.08), and was independently predicted by relative wall thickness and receipt of TAVR. LVEF improvement with standard therapy portended reduced all-cause mortality at 1?year (28.6% vs 65.6% without LVEF improvement; HR=0.32 (95% CI 0.11 to 0.93); p=0.03) but not at 2?years.In inoperable patients with severe AS, mild-to-moderate LV dysfunction is associated with higher cardiac mortality with standard therapy but not TAVR. A subset of patients undergoing standard therapy with LV dysfunction demonstrates LVEF improvement and favourable 1-year but not 2-year survival. TAVR improves survival and should be considered the standard of care for inoperable patients with AS and LVEF >20%.ClinicalTrials.gov Unique Identifier #NCT00530894.

Abstract

The aim of this study was to determine the impact of downstream coronary stenosis in the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) on the assessment of fractional flow reserve (FFR) across an intermediate left main coronary artery (LMCA) stenosis in humans with the pressure wire positioned in the nondiseased downstream vessel.Accurate assessment of intermediate LMCA disease is critical for guiding decisions regarding revascularization. In theory, FFR across an intermediate LMCA stenosis will be affected by downstream disease, even if the pressure wire is positioned in the nondiseased downstream vessel.After percutaneous coronary intervention of the LAD, LCx, or both, an intermediate LMCA stenosis was created with a deflated balloon catheter. FFR was measured in the LAD and LCx coronary arteries before and after creation of downstream stenosis by inflating an angioplasty balloon within the newly placed stent. The true FFR (FFRtrue) of the LMCA, measured in the nondiseased downstream vessel in the absence of stenosis in the other vessel, was compared with the apparent FFR (FFRapp) measured in the presence of stenosis.In 25 patients, 91 pairs of measurements were made, 71 with LAD stenosis and 20 with LCx stenosis. FFRtrue of the LMCA was significantly lower than FFRapp (0.81 ± 0.08 vs. 0.83 ± 0.08, p < 0.001), although the numerical difference was small. This difference correlated with the severity of the downstream disease (r = 0.35, p < 0.001). In all cases in which FFRapp was >0.85, FFRtrue was >0.80.In most cases, downstream disease does not have a clinically significant impact on the assessment of FFR across an intermediate LMCA stenosis with the pressure wire positioned in the nondiseased vessel.

Abstract

Bifurcation lesions are frequent among patients with symptomatic coronary disease treated by percutaneous coronary intervention. Current evidence recommends a conservative (provisional) approach when treating the side branch (SB).The TRYTON (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries) bifurcation trial sought to compare treatment of de novo true bifurcation lesions using a dedicated bifurcation stent or SB balloon angioplasty.We randomly assigned patients with true bifurcation lesions to a main vessel stent plus provisional stenting or the bifurcation stent. The primary endpoint (powered for noninferiority) was target vessel failure (TVF) (cardiac death, target vessel myocardial infarction, and target vessel revascularization). The secondary angiographic endpoint (powered for superiority) was in-segment percent diameter stenosis of the SB at 9 months.We randomized 704 patients with bifurcation coronary lesions at 58 centers (30 from Europe and 28 from the United States). At 9 months, TVF was 17.4% in the bifurcation stent group compared with 12.8% in the provisional group (p = 0.11), mainly because of a higher periprocedural myocardial infarction rate (13.6% vs. 10.1%, p = 0.19). The TVF difference of +4.6% (2-sided 95% confidence interval: -1.0 to 10.3; upper limit of the 1-sided 95% confidence interval: 10.3) was not within the pre-specified noninferiority margin of 5.5% (p = 0.42 for noninferiority). The SB in-segment diameter stenosis among the angiographic cohort was lower in the bifurcation stent group compared with the provisional group (31.6% vs. 38.6%, p = 0.002 for superiority), with no difference in binary restenosis rates (diameter stenosis ?50%) at 9 months follow-up (22.6% vs. 26.8%, p = 0.44).Provisional stenting should remain the preferred strategy for treatment of non-left main true coronary bifurcation lesions. (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [TRYTON]; NCT01258972).

Abstract

The logistic European System for Cardiac Operative Risk Evaluation (LES) score and the Society of Thoracic Surgeons (STS) score are validated to predict 30-day outcomes following surgical aortic valve replacement (SAVR) with or without coronary artery bypass grafting. Their performance when applied to patients undergoing transcatheter aortic valve replacement (TAVR) is controversial.We compared predicted and observed 30-day/in-hospital and 1-year mortality of patients undergoing TAVR in the first Placement of Aortic Transcatheter Valves trial and continued access registry (N = 2466). The performance of the LES and STS scores (prospectively calculated) was evaluated using standard assessments of discrimination and calibration. Performance of STS and LES scores among 307 patients undergoing SAVR from the high-risk cohort of the randomized trial were also examined.In patients undergoing TAVR, the observed 30-day/in-hospital mortality was 6.5%, whereas the predicted 30-day mortality was higher by both STS score (11.4% ± 3.9%) and LES score (26.6% ± 16.2%). The discrimination for both scores was poor for 30-day/in-hospital and 1-year mortality. Calibration was better for STS score than for LES at 1 year but poor for both at 30 days among TAVR cohort. These results were consistent among the subgroups of patients undergoing transfemoral and transapical access; however, the STS score had better performance among the high-risk patients who underwent SAVR at 30 days but not 1 year.The STS and LES surgical risk scores overestimated 30-day/in-hospital mortality and were poor discriminators of post-TAVR mortality, but the calibration of the STS score was better in these high-risk patients. These data highlight the need for TAVR-specific risk models to optimize patient selection.

Abstract

The logistic European System for Cardiac Operative Risk Evaluation (LES) score and the Society of Thoracic Surgeons (STS) score are validated to predict 30-day outcomes following surgical aortic valve replacement (SAVR) with or without coronary artery bypass grafting. Their performance when applied to patients undergoing transcatheter aortic valve replacement (TAVR) is controversial.We compared predicted and observed 30-day/in-hospital and 1-year mortality of patients undergoing TAVR in the first Placement of Aortic Transcatheter Valves trial and continued access registry (N = 2466). The performance of the LES and STS scores (prospectively calculated) was evaluated using standard assessments of discrimination and calibration. Performance of STS and LES scores among 307 patients undergoing SAVR from the high-risk cohort of the randomized trial were also examined.In patients undergoing TAVR, the observed 30-day/in-hospital mortality was 6.5%, whereas the predicted 30-day mortality was higher by both STS score (11.4% ± 3.9%) and LES score (26.6% ± 16.2%). The discrimination for both scores was poor for 30-day/in-hospital and 1-year mortality. Calibration was better for STS score than for LES at 1 year but poor for both at 30 days among TAVR cohort. These results were consistent among the subgroups of patients undergoing transfemoral and transapical access; however, the STS score had better performance among the high-risk patients who underwent SAVR at 30 days but not 1 year.The STS and LES surgical risk scores overestimated 30-day/in-hospital mortality and were poor discriminators of post-TAVR mortality, but the calibration of the STS score was better in these high-risk patients. These data highlight the need for TAVR-specific risk models to optimize patient selection.

Abstract

Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcomes compared with an angiography-guided strategy in patients with multivessel coronary artery disease (CAD). However, the effect of age on FFR has not been well-studied. We aimed to evaluate the impact of age on the favorable results of routine FFR-guided PCI for multivessel CAD.We compared 1 year outcomes between FFR-guided PCI and angiography-guided PCI in the 512 patients enrolled in the FAME study <65 years old compared to the 493 patients ? 65 years old. We also evaluated the effect of age on the FFR result of varying degrees of visually estimated coronary stenosis.The 1-year rate of death, myocardial infarction or repeat revascularization in the angiography-guided group tended to be higher than in the FFR-guided group for both those patients <65 (17.2% vs. 12.0%, P = 0.098) and those ? 65 years old (19.7% vs. 14.3%, P = 0.111) with no significant interaction based on age (P = 0.920). Older patients had higher FFR in vessels with 50% to 70% stenosis (0.83 ± 0.11 vs. 0.80 ± 0.13, P = 0.028) and in vessels with 71% to 90% stenosis (0.69 ± 0.15 vs. 0.65 ± 0.16, P = 0.002). The proportion of functionally significant lesions (FFR ? 0.80) in vessels with 71% to 90% stenosis was significantly lower in elderly compared to younger patients (75.3% vs. 84.1%, P = 0.013).FFR-guided PCI is beneficial regardless of age, however, older patients have fewer functionally significant lesions, despite a similar angiographic appearance.

Abstract

Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

Abstract

Invasive evaluation and treatment of coronary artery disease (CAD) has traditionally been based upon coronary angiography to determine the need for and the success of revascularization. However, coronary angiography augmented with fractional flow reserve (FFR) creates a paradigm shift, providing a more complete functional assessment of coronary lesions. Measuring FFR to identify ischemic lesions and guide revascularization results in fewer adverse outcomes, including persistent angina, myocardial infarction, and mortality. An ischemic lesion identified by FFR is more likely to lead to adverse events when compared with an angiographically similar lesion with nonischemic FFR when both are treated medically. Although the mechanism explaining this is unclear, it is likely multifactorial, including the impact of mechanical forces, upregulation of inflammatory mediators, and the amount of distal myocardial tissue at risk. Using both anatomic and ischemia-guided assessments (such as the Functional SYNTAX Score) aids in the therapeutic decision-making process in patients with multivessel CAD. This review focuses on the evidence for FFR-guided management of multivessel CAD.

Abstract

The aim of this article is to review what is currently known about fractional flow reserve (FFR) and related coronary physiological indices in patients with acute coronary syndrome (ACS) including non-ST-elevation (NSTEMI) and ST-elevation myocardial infarction (STEMI) with a view to making recommendations for daily practice.We explored all relevant publications to date including literature reviews, clinical trials and registries. We identified sufficient data on FFR in the setting of NSTEMI to confirm it to be a reliable and useful tool for lesion-level decision making with certain pitfalls as outlined below. There was limited published literature on FFR in STEMI. However, there is some evidence that, in patients who are stable after culprit lesion intervention, FFR may be of value for assessing the functional significance of non-culprit lesions. When measured in the culprit artery of patients with STEMI, the index of myocardial resistance (IMR) predicts long-term clinical outcomes.In patients with ACS, there is an increasing evidence base to support the role of FFR to guide revascularisation and of IMR to predict outcome.

Abstract

Cardiac conduction disturbances, including a left bundle branch block (LBBB), occur frequently following transcatheter aortic valve replacement (TAVR) and may be associated with adverse clinical events. This analysis examines the incidence and implications of new onset, persistent LBBB in patients undergoing TAVR with a balloon-expandable valve.Patients undergoing TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) trial and continued access registries with baseline and discharge/7-day electrocardiograms were included. Prior permanent pacemaker implantation (PPI) and baseline intraventricular conduction abnormalities were exclusion criteria. Predictors of new LBBB were identified and outcomes compared between patients with and without new LBBB. New LBBB occurred in 121 of 1151 (10.5%) patients and persisted in more than half at 6 months to 1 year. The only predictor of new LBBB was prior coronary artery bypass grafting. New LBBB was not associated with significant differences in 1-year mortality, cardiovascular mortality, repeat hospitalization, stroke, or myocardial infarction. However, it was associated with increased PPI during hospitalization (8.3 vs 2.8%, P = 0.005) and from discharge to 1 year (4.7 vs. 1.5%, P = 0.01). The ejection fraction failed to improve after TAVR in patients with new LBBB and remained lower at 6 months to 1 year (52.8 vs. 58.1%, P < 0.001).Persistent, new-onset LBBB occurred in 10.5% of patients without intraventricular baseline conduction who underwent TAVR in the PARTNER experience. New LBBB was not associated with death, repeat hospitalization, stroke, or myocardial infarction at 1 year, but was associated with a higher rate of PPI and failure of left ventricular ejection fraction to improve.

Abstract

This study sought to examine the diagnostic accuracy of the instantaneous wave-free ratio (iFR) and resting distal coronary artery pressure/aortic pressure (Pd/Pa) with respect to hyperemic fractional flow reserve (FFR) in a core laboratory-based multicenter collaborative study.FFR is an index of the severity of coronary stenosis that has been clinically validated in 3 prospective randomized trials. iFR and Pd/Pa are nonhyperemic pressure-derived indices of the severity of stenosis with discordant reports regarding their accuracy with respect to FFR.iFR, resting Pd/Pa, and FFR were measured in 1,768 patients from 15 clinical sites. An independent physiology core laboratory performed blinded off-line analysis of all raw data. The primary objectives were to determine specific iFR and Pd/Pa thresholds with ?90% accuracy in predicting ischemic versus nonischemic FFR (on the basis of an FFR cut point of 0.80) and the proportion of patients falling beyond those thresholds.Of 1,974 submitted lesions, 381 (19.3%) were excluded because of suboptimal acquisition, leaving 1,593 for final analysis. On receiver-operating characteristic analysis, the optimal iFR cut point for FFR ?0.80 was 0.90 (C statistic: 0.81 [95% confidence interval: 0.79 to 0.83]; overall accuracy: 80.4%) and for Pd/Pa was 0.92 (C statistic: 0.82 [95% confidence interval: 0.80 to 0.84]; overall accuracy: 81.5%), with no significant difference between these resting measures. iFR and Pd/Pa had ?90% accuracy to predict a positive or negative FFR in 64.9% (62.6% to 67.3%) and 48.3% (45.6% to 50.5%) of lesions, respectively.This comprehensive core laboratory analysis comparing iFR and Pd/Pa with FFR demonstrated an overall accuracy of ~80% for both nonhyperemic indices, which can be improved to ?90% in a subset of lesions. Clinical outcome studies are required to determine whether the use of iFR or Pd/Pa might obviate the need for hyperemia in selected patients.

Abstract

To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery.Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium.In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery.IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route.Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.

Abstract

We evaluated the potential effects of granulocyte colony-simulating factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart transplant recipients.Of 247 patients undergoing heart transplantation from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC] <2.5 × 10(9)cells/L) in the absence of active infection, rejection, or malignancy. In 24 (46%) patients a clinical decision was made to treat the leukopenia with G-CSF (G-CSF group), and 28 (54%) Patients received no G-CSF (non-GCSF group). Patients followed up for 1 year after the period of leukopenia were assessed for allograft vasculopathy and acute rejection incidence.At baseline, the G-CSF group and the non-GCSF group did not differ in age, gender, race, heart failure etiology, creatinine, left ventricular ejection fraction (LVEF) or immunosupressive regimen. During 1-year follow-up there were no deaths in the G-CSF group, and 1 death in the non-GCSF group (P = .34). The incidence of rejection or progressive allograft vasculopathy was lower in the G-CSF group when compared with the non-GCSF group (2 [8%] vs 15 [53%]; P < .01). Multivariate analysis identified both prior rejection episodes and G-CSF therapy as factors associated with the combined end-point of rejection or progressive allograft vasculopathy (odds ratio [OR] = 7.89 [1.67-37.2] and OR = 0.09 [0.02-0.52], respectively).G-CSF therapy appears to be associated with a decreased incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients, suggesting a potential immunomodulatory effect of G-CSF.

Abstract

When selecting coronary stenoses for interventional treatment, assessment of reversible ischaemia is paramount from a symptomatic as well as prognostic point of view. Fractional flow reserve (FFR) is now considered the gold standard for invasive assessment of ischaemia. By measuring FFR in the catheterization laboratory, one can accurately identify which lesions should be stented resulting in improved patient outcome in most elective clinical and angiographic conditions. Recently, in the European Society of Cardiology guidelines on coronary revascularization, FFR was upgraded to an IA classification in multivessel percutaneous coronary intervention. In this review paper, the rationale for routine measurement of FFR will be reviewed and studies supporting its integration into everyday practice will be highlighted.

Abstract

This study sought to compare fractional flow reserve (FFR) with the instantaneous wave-free ratio (iFR) in patients with coronary artery disease and also to determine whether the iFR is independent of hyperemia.FFR is a validated index of coronary stenosis severity. FFR-guided percutaneous coronary intervention (PCI) improves clinical outcomes compared to angiographic guidance alone. iFR has been proposed as a new index of stenosis severity that can be measured without adenosine.We conducted a prospective, multicenter, international study of 206 consecutive patients referred for PCI and a retrospective analysis of 500 archived pressure recordings. Aortic and distal coronary pressures were measured in duplicate in patients under resting conditions and during intravenous adenosine infusion at 140 ?g/kg/min.Compared to the FFR cut-off value of ?0.80, the diagnostic accuracy of the iFR value of ?0.80 was 60% (95% confidence interval [CI]: 53% to 67%) for all vessels studied and 51% (95% CI: 43% to 59%) for those patients with FFR in the range of 0.60 to 0.90. iFR was significantly influenced by the induction of hyperemia: mean ± SD iFR at rest was 0.82 ± 0.16 versus 0.64 ± 0.18 with hyperemia (p < 0.001). Receiver operating characteristics confirmed that the diagnostic accuracy of iFR was similar to resting Pd/Pa and trans-stenotic pressure gradient and significantly inferior to hyperemic iFR. Analysis of our retrospectively acquired dataset showed similar results.iFR correlates weakly with FFR and is not independent of hyperemia. iFR cannot be recommended for clinical decision making in patients with coronary artery disease.

Abstract

This study sought to examine the clinical performance of and theoretical basis for the instantaneous wave-free ratio (iFR) approximation to the fractional flow reserve (FFR).Recent work has proposed iFR as a vasodilation-free alternative to FFR for making mechanical revascularization decisions. Its fundamental basis is the assumption that diastolic resting myocardial resistance equals mean hyperemic resistance.Pressure-only and combined pressure-flow clinical data from several centers were studied both empirically and by using pressure-flow physiology. A Monte Carlo simulation was performed by repeatedly selecting random parameters as if drawing from a cohort of hypothetical patients, using the reported ranges of these physiologic variables.We aggregated observations of 1,129 patients, including 120 with combined pressure-flow data. Separately, we performed 1,000 Monte Carlo simulations. Clinical data showed that iFR was +0.09 higher than FFR on average, with ±0.17 limits of agreement. Diastolic resting resistance was 2.5 ± 1.0 times higher than mean hyperemic resistance in patients. Without invoking wave mechanics, classic pressure-flow physiology explained clinical observations well, with a coefficient of determination of >0.9. Nearly identical scatter of iFR versus FFR was seen between simulation and patient observations, thereby supporting our model.iFR provides both a biased estimate of FFR, on average, and an uncertain estimate of FFR in individual cases. Diastolic resting myocardial resistance does not equal mean hyperemic resistance, thereby contravening the most basic condition on which iFR depends. Fundamental relationships of coronary pressure and flow explain the iFR approximation without invoking wave mechanics.

Abstract

Several studies have shown that fractional flow reserve (FFR) measurement can aid in the assessment of left main coronary stenosis. However, the impact of downstream epicardial stenosis on left main FFR assessment with the pressure wire in the nonstenosed downstream vessel remains unknown.Variable stenoses were created in the left main coronary arteries and downstream epicardial vessels in 6 anaesthetized male sheep using balloon catheters. A total of 220 pairs of FFR assessments of the left main stenosis were obtained, before and after creation of a stenosis in a downstream epicardial vessel, by having a pressure-sensor wire in the other nonstenosed downstream vessel. The apparent left main FFR in the presence of downstream stenosis (FFR(app)) was significantly higher compared with the true FFR in the absence of downstream stenosis (FFR(true); 0.80±0.05 versus 0.76±0.05; estimate of the mean difference, 0.035; P<0.001). The difference between FFR(true) and FFR(app) correlated with composite FFR of the left main plus stenosed artery (r=-0.31; P<0.001) indicating that this difference was greater with increasing epicardial stenosis severity. Among measurements with FFR(app) >0.80, 9% were associated with an FFR(true) of <0.75. In all instances, the epicardial lesion was in the proximal portion of the stenosed vessel, and the epicardial FFR (combined FFR of the left main and downstream stenosed vessel) was ?0.50.A clinically relevant effect on the FFR assessment of left main disease with the pressure wire in a nonstenosed downstream vessel occurs only when the stenosis in the other vessel is proximal and very severe.

Abstract

The presentation, mechanisms, and incidence of ST elevation myocardial infarction (STEMI) in heart transplant recipients have been characterized only to a limited degree in the current literature. Herein, we present a unique case of STEMI years after heart transplantation with a focus on the salient features of its diagnosis and interventions. We also provide a review of the epidemiology of this phenomenon.A 33-year-old woman who was status post cardiac transplantation for dilated cardiomyopathy presented to the clinic with mild nonspecific fatigue and concern after having noticed relative bradycardia compared with her posttransplantation baseline heart rate. Electrocardiogram (ECG) showed junctional rhythm and inferior ST elevations, likely reflecting nodal ischemia. Troponins were grossly positive and echocardiogram showed marked right ventricular dysfunction.Successful percutaneous coronary intervention (PCI) with aspiration thrombectomy and drug-eluting stent placement was emergently performed. The heart's rhythm soon returned to sinus tachycardia. Right ventricular wall-motion abnormalities resolved. The patient suffered no clinical sequelae of her STEMI.This case illustrated that "classic" symptoms of STEMI may not occur at all in the setting of heart transplantation. To our knowledge, this is the first case of posttransplantation STEMI presenting as asymptomatic bradycardia, and highlights the importance of maintaining high clinical suspicion for ischemia in transplant recipients with subtle changes. In reviewing the epidemiology of this case, we locate and bundle different types of studies that have directly or indirectly looked at STEMI in heart transplantation. For a variety of putative pathophysiological reasons, STEMI is indeed a rare manifestation of the common transplant phenomenon of coronary artery vasculopathy (CAV).

Abstract

When invasively assessing coronary artery disease, the primary goal should be to determine whether the disease is causing a patient's symptoms and whether it is likely to cause future cardiac events. The presence of myocardial ischemia is our best gauge of whether a lesion is responsible for symptoms and likely to result in a future cardiac event. In the catheterization laboratory, fractional flow reserve (FFR) measured with a coronary pressure wire is the reference standard for identifying ischemia-producing lesions. Its spatial resolution is unsurpassed with it not only being vessel-specific, but also lesion-specific. There is now a wealth of data supporting the accuracy of measuring FFR to identify ischemia-producing lesions. FFR-guided percutaneous coronary intervention of these lesions results in improved outcomes and saves resources. Non-hemodynamically significant lesions can be safely managed medically with a low rate of subsequent cardiac events.

Abstract

This study sought to investigate a novel method to calculate the index of microcirculatory resistance (IMR) in the presence of significant epicardial stenosis without the need for balloon dilation to measure the coronary wedge pressure (P(w)).The IMR provides a quantitative measure of coronary microvasculature status. However, in the presence of significant epicardial stenosis, IMR calculation requires incorporation of the coronary fractional flow reserve (FFR(cor)), which requires balloon dilation within the coronary artery for P(w) measurement.A method to calculate IMR by estimating FFR(cor) from myocardial FFR (FFR(myo)), which does not require P(w) measurement, was developed from a derivation cohort of 50 patients from a single institution. This method to calculate IMR was then validated in a cohort of 72 patients from 2 other different institutions. Physiology measurements were obtained with a pressure-temperature sensor wire before coronary intervention in both cohorts.From the derivation cohort, a strong linear relationship was found between FFR(cor) and FFR(myo) (FFR(cor) = 1.34 × FFR(myo) - 0.32, r(2) = 0.87, p < 0.001) by regression analysis. With this equation to estimate FFR(cor) in the validation cohort, there was no significant difference between IMR calculated from estimated FFR(cor) and measured FFR(cor) (21.2 ± 12.9 U vs. 20.4 ± 13.6 U, p = 0.161). There was good correlation (r = 0.93, p < 0.001) and agreement by Bland-Altman analysis between calculated and measured IMR.The FFR(cor), and, by extension, microcirculatory resistance can be derived without the need for P(w). This method enables assessment of coronary microcirculatory status before or without balloon inflation, in the presence of epicardial stenosis.

Abstract

Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients.Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization, and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance. The presence of microvascular dysfunction, predefined by an index of microcirculatory resistance >20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year, with odds ratio of 4.0 (1.3-12.8) and 3.6 (1.2-11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1±0.7 versus 3.5±0.7 L/min per m(2); P=0.02) and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices ([0.54±0.09 versus 0.43±0.09; P<0.01] and [0.47±0.14 versus 0.32±0.05; P<0.01], respectively). Microvascular dysfunction was also associated with a higher likelihood of death, graft failure, or allograft vasculopathy at 5 years after transplant (hazard ratio, 2.52 [95% CI, 1.04-5.91]).A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using index of microcirculatory resistances at 1 year was also associated with worse graft function and possibly worse clinical outcomes.

Abstract

The aim of this study was to assess the validity of measuring fractional flow reserve (FFR) of the left main (LM) coronary artery in the setting of concomitant left anterior descending (LAD) or left circumflex (LCX) stenoses.The theoretical impact of a stenosis in the LAD on the FFR assessment of intermediate LM disease with the pressure wire in an unobstructed LCX is currently unknown.A previously validated in vitro model of the coronary circulation was used to create a fixed intermediate stenosis of the LM and a variable downstream LAD or LCX stenosis. The true LM FFR (FFR(LM true)), with no concomitant downstream disease, was compared to the apparent LM FFR (FFR(LM apparent)), with concomitant downstream disease measured with different degrees of LAD or LCX disease. Additionally, an equation based on a resistors model was derived to predict the effect of downstream stenosis on LM FFR (FFR(LM predicted)).In the setting of isolated moderate LM disease (FFR 0.72 ± 0.08), mild to moderate proximal LAD or LCX lesions did not significantly affect LM FFR. Lesions with a composite FFR (LM + downstream disease) ?0.65 resulted in an FFR(LM apparent) that was not significantly different from FFR(LM true) (0.76 ± 0.06 vs. 0.76 ± 0.05, p = 0.124). Our equation for FFR(LM predicted) accurately modeled the effects of concomitant disease (r = 0.95, p < 0.001).These data suggest that in the presence of proximal mild to moderate LAD or LCX disease, LM FFR can be reliably measured with the pressure wire placed in the uninvolved epicardial artery.

Abstract

This study sought to evaluate the impact of sex differences on fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI).The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study demonstrated that FFR-guided PCI improves outcomes compared with an angiography-guided strategy. The role of FFR-guided PCI in women versus men has not been evaluated.We analyzed 2-year data from the FAME study in the 744 men and 261 women with multivessel coronary disease, who were randomized to angiography- or FFR-guided PCI. Statistical comparisons based on sex were stratified by treatment method.Although women were older and had significantly higher rates of hypertension than men did, there were no differences in the rates of major adverse cardiac events (20.3% vs. 20.2%, p = 0.923) and its individual components at 2 years. FFR values were significantly higher in women than in men (0.75 ± 0.18 vs. 0.71 ± 0.17, p = 0.001). The proportion of functionally significant lesions (FFR ? 0.80) was lower in women than in men for lesions with 50% to 70% stenosis (21.1% vs. 39.5%, p < 0.001) and for lesions with 70% to 90% stenosis (71.9% vs. 82.0%, p = 0.019). An FFR-guided strategy resulted in similar relative risk reductions for death, myocardial infarction, and repeat revascularization in men and in women. There were no interactions between sex and treatment method for any outcome variables.In comparison with men, angiographic lesions of similar severity are less likely to be ischemia-producing in women. An FFR-guided PCI strategy is equally beneficial in women as it is in men.

Abstract

This study sought to identify incidence, predictors, and impact of vascular complications (VC) after transfemoral (TF) transcatheter aortic valve replacement (TAVR).VC after TF-TAVR are frequent and may be associated with unfavorable prognosis.From the randomized controlled PARTNER (Placement of AoRTic TraNscathetER Valve) trial, a total of 419 patients (177 from cohort B [inoperable] and 242 from cohort A [operable high-risk]) were randomly assigned to TF-TAVR and actually received the designated treatment. First-generation Edwards-Sapien valves and delivery systems were used, via a 22- or 24-F sheath. The 30-day rates of major and minor VC (modified Valve Academic Research Consortium definitions), predictors, and effect on 1-year mortality were assessed.Sixty-four patients (15.3%) had major VC and 50 patients (11.9%) had minor VC within 30 days of the procedure. Among patients with major VC, vascular dissection (62.8%), perforation (31.3%), and access-site hematoma (22.9%) were the most frequent modes of presentation. Major VC, but not minor VC, were associated with significantly higher 30-day rates of major bleeding, transfusions, and renal failure requiring dialysis, and with a significantly higher rate of 30-day and 1-year mortality. The only identifiable independent predictor of major VC was female gender (hazard ratio [HR]: 2.31 [95% confidence interval (CI): 1.08 to 4.98], p = 0.03). Major VC (HR: 2.31 [95% CI: 1.20 to 4.43], p = 0.012), and renal disease at baseline (HR: 2.26 [95% CI: 1.34 to 3.81], p = 0.002) were identified as independent predictors of 1-year mortality.Major VC were frequent after TF-TAVR in the PARTNER trial using first-generation devices and were associated with high mortality. However, the incidence and impact of major VC on 1-year mortality decreased with lower-risk populations.

Abstract

Periprocedural myocardial infarction (MI) occurs in a significant proportion of patients undergoing percutaneous coronary intervention (PCI) and portends poor outcomes. Currently, no clinically applicable method predicts periprocedural MI in the cardiac catheterization laboratory before it occurs. We hypothesized that impaired baseline coronary microcirculatory reserve, which reduces the ability to tolerate ischemic insults, is a risk for periprocedural MI and that the index of microcirculatory resistance (IMR) measured during PCI can predict occurrence of periprocedural MI.Consecutive patients undergoing elective PCI of a single lesion in the left anterior descending coronary artery were recruited. A pressure-temperature sensor wire was used to measure IMR before PCI. Of the 50 patients studied, 10 had periprocedural MI. From binary logistic regression analyses of all clinical, procedural, and physiological parameters, univariable predictors of periprocedural MI were pre-PCI IMR (P=0.003) and the number of stents used (P=0.039). Pre-PCI IMR was the only independent predictor in bivariable regression analyses performed by adjusting for each available covariate one at a time (all P?0.02). Pre-PCI IMR ?27 U had 80.0% sensitivity and 85.0% specificity for predicting periprocedural MI (C statistic, 0.80; P=0.003). Pre-PCI IMR ?27 U was independently associated with a 23-fold risk of developing periprocedural MI (odds ratio, 22.7; 95% CI, 3.8-133.9).These data suggest that the status of the coronary microcirculation plays a role in determining susceptibility toward periprocedural MI at the time of elective PCI. The IMR can predict subsequent risk of developing myocardial necrosis and may guide adjunctive prevention strategies.

Abstract

Retroperitoneal hematoma (RPH) increases morbidity and mortality in percutaneous coronary intervention (PCI). High femoral arteriotomy is an independent predictor of RPH, but the optimal angiographic criterion for defining a high puncture is unknown.We retrospectively identified 557 consecutive PCI cases with femoral angiograms. Arteriotomy sites were categorized as high based on three angiographic criteria: at or above the proximal third of the femoral head (criterion A), at or above the most inferior border of the inferior epigastric artery (criterion B), and at or above the origin of the inferior epigastric artery (criterion C). Cases of RPH were then identified.Of the 557 PCI patients, 26 had a high femoral arteriotomy by criterion A, 17 by criterion B, and 6 by criterion C. Among these patients with a high arteriotomy, RPH occurred in four with criterion A, in three with criterion B, and in one with criterion C. Of the three criteria, criterion A most strongly correlated with RPH (odds ratio [OR] 96, 95% confidence interval [CI] 10.3-898.4; p < 0.0001) compared with criterion B (OR 58, 95% CI 8.9 to 372.6; p < 0.0001) or C (OR 27, 95% CI 2.6 to 290.1; p = 0.053). All criteria had high specificity (A, 96%; B, 97%; C, 99%), but the sensitivity was higher with criterion A (80%) than criterion B (60%) or C (20%), and statistically, the use of criterion A led to the most accurate risk-stratification for RPH (A, ? = 0.79; B, ? = 0.59; C, ? = 0.19).Among the three common definitions of high arteriotomy, femoral artery puncture at or above the proximal third of the femoral head is the landmark that most accurately risk stratifies PCI patients for development of RPH.

Abstract

This study sought to assess the effectiveness and safety of the second-generation frequency-domain optical coherence tomography (FD-OCT) system.The second-generation FD-OCT was recently developed, with simplified imaging technique and faster acquisition time compared to the first-generation time-domain OCT. However, the safety and effectiveness of the FD-OCT has not been evaluated, and this study was conceived as a preapproval study for Food and Drug Administration clearance for clinical use in the United States.A total of 50 patients were enrolled from 3 institutions. Following stent implantation, the FD-OCT was performed with contrast injection through the guiding catheter to acquire pullback images with the pressure-triggered automatic pullback device. The primary endpoint was to achieve a median clear image length of more than 24 mm. Serious procedure-related or postprocedural adverse events (death, myocardial infarction, or ventricular arrhythmia) were recorded to assess safety of the device.The primary endpoint of obtaining >24 mm of median clear image length (CIL) was achieved in 94% of the subjects (47 out of 50), with measured CIL of 43.2 mm. In 5 patients (10.6%), a second attempt was necessary due to suboptimal image quality of the first pullback. In 36 patients (76.6%), a full stent length was obtained during the first attempt. There were no serious procedure-related or postprocedural adverse events.The new second-generation FD-OCT system provides fast and reliable resolution images of the coronary artery. The pullback can be safely performed over long segments of the artery without serious adverse events.

Abstract

Recent studies show that coronary microcirculatory impairment is an independent predictor of poor outcomes in patients with cardiovascular disease. However, controversy exists over whether microcirculatory resistance, a measure of coronary microcirculatory status, is dependent on epicardial stenosis severity. Previous studies demonstrating that microcirculatory resistance is dependent on epicardial stenosis severity have not accounted for collateral flow in their measurement of microcirculatory resistance. We investigated whether the index of microcirculatory resistance is independent of epicardial stenosis by comparing the index of microcirculatory resistance (IMR) levels in patients before and after percutaneous coronary intervention (PCI).Consecutive patients undergoing elective PCI of the left anterior descending artery were recruited. Patients who developed periprocedural myocardial infarction were excluded. A pressure-temperature sensor wire was used to measure the apparent IMR (IMR(app)), which does not adjust for collateral flow, and the true IMR (IMR(true)), which incorporates wedge pressure measurement to account for collateral flow, before and after PCI. In 43 patients, there was no difference between pre- and post-PCI IMR(true) (mean difference=0.8±11.7, P=0.675). IMR(app) was higher pre-PCI compared with post-PCI (mean difference=10.0±14.5, P<0.001). IMR(app) was higher than IMR(true) (mean difference=9.3±14.2, P<0.001), and the difference between the IMR(app) and IMR(true) became greater with decreasing fractional flow reserve and increasing coronary wedge pressure. Pre-PCI fractional flow reserve correlated modestly with IMR(app) (r=-0.33, P=0.03), but not IMR(true) (r=0.26, P=0.10).Coronary microcirculatory resistance is independent of functional epicardial stenosis severity when collateral flow is taken into account.

Abstract

There are conflicting data as to the prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) being assessed for liver transplantation (LT). The aims of this study were to compare the prevalence of CAD in patients with alcohol-related versus non-alcohol-related ESLD and to assess the diagnostic utility of dobutamine stress echocardiography (DSE) in predicting angiographically important CAD. Consecutive patients with ESLD being assessed for LT (n = 420, mean age 56 ± 8 years) were identified and divided into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE, and coronary angiographic characteristics were recorded. There were no significant differences in age or CAD risk factors between groups. The incidence of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the presence of ?1 CAD risk factor was associated with significant CAD (p <0.05 for all). Absence of cardiac risk factors was highly predictive in ruling out angiographically significant disease (negative predictive value 100% for alcohol-related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205 patients. In the 2 groups, DSE had poor predictive value for diagnosing significant CAD but was useful in ruling out patients without significant disease (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol-related ESLD). In conclusion, there was a significantly lower prevalence of severe CAD in patients with alcohol-related ESLD. These findings suggest that invasive coronary angiography may not be necessary in this subgroup, particularly in the absence of CAD risk factors and negative results on DSE.

Abstract

The aim of this study was to study whether there is a difference in benefit of fractional flow reserve (FFR) guidance for percutaneous coronary intervention (PCI) in multivessel coronary disease in patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI), compared with stable angina (SA).The use of FFR to guide PCI has been well established for patients with SA. Its use in patients with UA or NSTEMI has not been investigated prospectively.In the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study 1,005 patients with multivessel disease amenable to PCI were included and randomized to either angiography-guided PCI of all lesions ?50% or FFR-guided PCI of lesions with an FFR ?0.80. Patients admitted for UA or NSTEMI with positive troponin but total creatine kinase <1,000 U/l were eligible for inclusion. We determined 2-year major adverse cardiac event rates of these patients and compared it with stable patients.Of 1,005 patients, 328 had UA or NSTEMI. There was no evidence for heterogeneity among the subgroups for any of the outcome variables (all p values >0.05). Using FFR to guide PCI resulted in similar risk reductions of major adverse cardiac events and its components in patients with UA or NSTEMI, compared with patients with SA (absolute risk reduction of 5.1% vs. 3.7%, respectively, p = 0.92). In patients with UA or NSTEMI, the number of stents was reduced without increase in hospital stay or procedure time and with less contrast use, in similarity to stable patients.The benefit of using FFR to guide PCI in multivessel disease does not differ between patients with UA or NSTEMI, compared with patients with SA.

Abstract

We sought to evaluate the variability in the assessment of jailed side branch (SB) lesions by visual estimation and quantitative coronary angiography (QCA) and to compare those results with fractional flow reserve (FFR).Twenty jailed SB lesions with available FFR (median 0.76; range, 0.39-0.94) were selected from the PRESSURE trial. Lesions were assessed by three independent QCA core laboratories with different QCA systems and by three different cardiologist groups (five European bifurcation club members, five Korean experts, and five trainees). Agreements of the continuous measurements were expressed as the intraclass correlation coefficient (ICC) and average coefficient of variance (CV), and those of the categorical values as kappa.Mean minimum lumen diameter (MLD) and % diameter stenosis differed among the three QCA systems up to 0.30 mm and 9.65%, respectively (P < 0.001). Three QCA systems showed fair agreement for the measurements of reference diameter, % diameter stenosis, MLD, and lesion length (ICC 0.346-0.686, CV 8.7-29.5%), and a poor agreement on stenosis of 75% or more (Fleiss ? 0.14 and mean ? 0.18). Agreements of visual estimation among the three groups were poor to fair (Fleiss ? 0.167-0.367). Sensitivity and specificity for predicting ischemia-inducible lesion (FFR < 0.75) were 64.7% and 48.0% for visual estimation and 56.6% and 56.6% by QCA, respectively. Visual estimation overestimated the % diameter stenosis and functional significance of the lesions compared with QCA (P < 0.001) and FFR (P = 0.036).Angiographic assessment of jailed SB lesions by both QCA and visual estimation showed variability. Visual estimation tended to overestimate the severity of jailed SB lesions compared to FFR and QCA.

Abstract

Although not a definitive treatment, percutaneous coronary intervention offers a palliative benefit to patients with cardiac allograft vasculopathy. Given the superior outcomes with drug-eluting stents (DESs) over bare metal stents (BMSs) in native coronary artery disease, similar improvements might be expected in transplant patients; however, the results have been mixed. Consecutive cardiac transplantation recipients at a single center receiving a stent for de novo cardiac allograft vasculopathy from 1997 to 2009 were retrospectively analyzed according to receipt of a DES versus a BMS. The angiographic and clinical outcomes were subsequently evaluated at 1 year. The baseline clinical and procedural characteristics were similar among those receiving DESs (n = 18) and BMSs (n = 16). Quantitative coronary angiography revealed no difference in the reference diameter, lesion length, or pre-/postprocedural minimal luminal diameter. At the 12-month angiographic follow-up visit, the mean lumen loss was significantly lower in the DES group than in the BMS group (0.19 ± 0.73 mm vs 0.76 ± 0.97 mm, p = 0.02). The DES group also had a lower rate of in-stent restenosis (12.5% vs 33%, p = 0.18), as well as a significantly lower rate of target lesion revascularization (0% vs 19%, p = 0.03). At 1 year, DESs were associated with a lower composite rate of cardiac death and nonfatal myocardial infarction (12% vs 38%, p = 0.04). In conclusion, DESs are safe and effective in the suppression of neointimal hyperplasia after percutaneous coronary intervention for cardiac allograft vasculopathy, resulting in significantly lower rates of late lumen loss and target lesion revascularization, as well as a reduced combined rate of cardiac death and nonfatal myocardial infarction.

Abstract

Saphenous vein grafts are commonly used conduits for surgical revascularization of coronary arteries but are associated with poor long-term patency rates. Percutaneous revascularization of saphenous vein grafts is associated with worse clinical outcomes including higher rates of in-stent restenosis, target vessel revascularization, myocardial infarction, and death compared with percutaneous coronary intervention of native coronary arteries. Use of embolic protection devices is a Class I indication according to the American College of Cardiology/American Heart Association guidelines to decrease the risk of distal embolization, no-reflow, and periprocedural myocardial infarction. Nonetheless, these devices are underused in clinical practice. Various pharmacological agents are available that may also reduce the risk of or mitigate the consequences of no-reflow. Covered stents do not decrease the rates of periprocedural myocardial infarction and restenosis. Most available evidence supports treatment with drug-eluting stents in this high-risk lesion subset to reduce angiographic and clinical restenosis, although large, randomized trials comparing drug-eluting stents and bare-metal stents are needed.

Abstract

The influence of donor-transmitted coronary atherosclerosis (DA) on plaque progression during the first year after cardiac transplantation (Tx) is unknown.Serial 3-dimensional intravascular ultrasound (IVUS) studies were performed within 8 weeks (baseline; BL) and at 1 year after Tx in 38 recipients. On the basis of maximum intimal thickness (MIT) at BL, recipients were divided into DA group (DA+; MIT?0.5 mm, n=23) or non-DA group (DA-; MIT<0.5 mm, n=15). Plaque, lumen, and vessel volume indexes were calculated by volume/measured length (mm/mm) in the left anterior descending artery. Univariate and multivariate regression analyses were attempted to reveal clinical predictors of change in coronary dimensions.During the first year after Tx, plaque volume index increased significantly in DA+ group, but did not change in DA- Group (DA+, 3.0±1.5 to 4.1±1.5 mm/mm, P<0.0001: DA-, 1.2±0.4 to 1.3±0.5 mm/mm, P=0.53). In both groups vessel volume index decreased significantly (DA+, 16.3±3.6 to 14.6±3.3 mm/mm, P=0.003: DA-, 13.5±4.1 to 12.0±3.3 mm/mm, P=0.01), as did lumen volume index (DA+, 13.2±3.1 to 10.5±2.7 mm/mm, P<0.0001: DA-, 12.2±3.7 to 10.7±3.0 mm/mm, P=0.004). Univariate and multivariate regression analyses revealed that DA was one of the strongest predictors for plaque progression.DA was associated with significant plaque progression during the first year after Tx, and in conjunction with negative remodeling, may be an important determinant of cardiac allograft vasculopathy.

Abstract

Patients still present with drug-eluting stent (DES) failure despite an angiographically successful implantation. The aim of the present study was to investigate the relation between the fractional flow reserve (FFR) measured after DES implantation and the clinical outcomes at 1 year. A total of 80 patients (mean age 62 years, 74% men, 99 DESs) underwent coronary pressure measurement at maximum hyperemia after successful DES implantation. The composite of major adverse cardiac events (MACE), including death, myocardial infarction, and ischemia-driven target vessel revascularization was evaluated at 1 year. The patients were divided into 2 groups (low-FFR group, FFR ?0.90 and high-FFR group, FFR >0.90) according to the median FFR. The mean poststent percent diameter stenosis was 11 ± 5% in the low-FFR group and 12 ± 3% in the high-FFR group (p = 0.31). Left anterior descending coronary artery lesions were more frequent in the low-FFR group than in the high-FFR group (82% vs 55%, p = 0.02). The mean stent length was greater in the low-FFR group than in the high-FFR group (38 ± 18 vs 28 ± 13 mm, p = 0.01). Six cases (7.5%) of MACE occurred during the 1-year follow-up. The rate of MACE was 12.5% in the low-FFR group and 2.5% in the high-FFR group (p <0.01). Receiver operating characteristic curves revealed 0.90 as the best cutoff of FFR after DES implantation for the prediction of 1-year MACE. In conclusion, a poststent FFR of ?0.90 correlated with a greater adverse event rate at 1 year.

Abstract

Discrepancy between angiographic percent (%) diameter stenosis and fractional flow reserve (FFR) exists in non-left main bifurcation lesions. The aim of this study was to compare angiographic stenosis severity and FFR in jailed ostial left circumflex artery (LCX) lesions after left main (LM)-to-left anterior descending artery (LAD) crossover stenting.Twenty-nine (n=29) patients with distal LM or ostial LAD lesions treated by LM-to-LAD crossover stenting were consecutively enrolled. After successful stenting, FFR was measured at the jailed LCX. Additional intervention was performed in lesions with FFR <0.8.The mean reference diameter of LCX was 3.1±0.4 mm, and percent diameter stenosis after crossover stenting was 56±21%. Angiographically significant stenosis (>50%) at the ostial LCX occurred in 59% (17/29) of cases. Among them, only five (29%) lesions had functional significance, and underwent additional procedure. During follow-up, three patients in the deferral group and two patients in the additional intervention group had target lesion revascularization.There was a discrepancy between angiographic percent diameter stenosis and FFR in jailed LCX lesions after LM crossover stenting.

Abstract

We report a patient who presents with acute chest pain and positive cardiac enzymes clinically consistent with an acute coronary syndrome (ACS). Coronary angiography revealed normal epicardial arteries and the left ventriculogram was notable for apical ballooning. This was strongly suggestive of takotsubo cardiomyopathy. Pressure wire measurements of Fractional flow reserve (FFR) and IMR demonstrated a normal FFR, but significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR, which unlike CFR is specific for the microcirculation and reproducible through a range of hemodynamic states.

Abstract

The present study evaluated the safety and efficacy of percutaneous coronary intervention (PCI) of the unprotected left main coronary artery (ULMCA) for the treatment of cardiac allograft vasculopathy (CAV) in consecutive unselected patients with orthotopic heart transplantation (OHT). PCI in patients with OHT and develop CAV has been associated with greater restenosis rates compared to PCI in patients with native coronary artery disease. A paucity of short- and long-term data is available from patients with OHT who have undergone PCI for ULMCA disease. The present retrospective, multicenter, international registry included 21 patients with OHT and CAV who underwent ULMCA PCI from 1997 to 2009. Angiographic success was achieved in all patients. Drug-eluting stents were used in 14 of the 21 patients. No major adverse cardiac events or repeat OHT occurred within the first 30 days. At a mean follow-up of 4.9 ± 3.2 years, 3 patients (14%) had died, myocardial infarction had occurred in 1 patient (5%), and target lesion revascularization had been required in 4 patients (19%). Follow-up angiography was performed in 16 patients (76%), and restenosis was observed in 4 (19%). No stent thrombosis of the ULMCA was observed. One patient (5%) underwent coronary artery bypass grafting, and 5 patients (24%) underwent repeat OHT. In conclusion, the results of our study have shown ULMCA PCI to be safe and reasonably effective in patients with OHT and represents a viable treatment strategy for CAV in these patients.

Abstract

The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) in patients with multivessel coronary artery disease (CAD).In patients with multivessel CAD undergoing PCI, coronary angiography is the standard method for guiding stent placement. The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year. It is unknown if these favorable results are maintained at 2 years of follow-up.At 20 U.S. and European medical centers, 1,005 patients with multivessel CAD were randomly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements. Before randomization, lesions requiring PCI were identified based on their angiographic appearance. Patients randomized to angiography-guided PCI underwent stenting of all indicated lesions, whereas those randomized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80, the rate of myocardial infarction was 0.2% and the rate of revascularization was 3.2 % after 2 years.Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infarction at 2 years when compared with standard angiography-guided PCI. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774).

Abstract

The purpose of this study was to investigate the relationship between angiographic and functional severity of coronary artery stenoses in the FAME (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation) study.It can be difficult to determine on the coronary angiogram which lesions cause ischemia. Revascularization of coronary stenoses that induce ischemia improves a patient's functional status and outcome. For stenoses that do not induce ischemia, however, the benefit of revascularization is less clear.In the FAME study, routine measurement of the fractional flow reserve (FFR) was compared with angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease. The use of the FFR in addition to angiography significantly reduced the rate of all major adverse cardiac events at 1 year. Of the 1,414 lesions (509 patients) in the FFR-guided arm of the FAME study, 1,329 were successfully assessed by the FFR and are included in this analysis.Before FFR measurement, these lesions were categorized into 50% to 70% (47% of all lesions), 71% to 90% (39% of all lesions), and 91% to 99% (15% of all lesions) diameter stenosis by visual assessment. In the category 50% to 70% stenosis, 35% were functionally significant (FFR 0.80). In the category 71% to 90% stenosis, 80% were functionally significant and 20% were not. In the category of subtotal stenoses, 96% were functionally significant. Of all 509 patients with angiographically defined multivessel disease, only 235 (46%) had functional multivessel disease (>or=2 coronary arteries with an FFR

Abstract

Although peri-strut low-intensity area (PLIA) is frequently observed on post-stenting optical coherence tomography (OCT) images, the histology associated with PLIA is undocumented.The 36 porcine coronary lesions treated with bare-metal (BMS: n=16) or drug-eluting (DES: n=20) stents were assessed by OCT and histology at 28 days. DES showed a significantly higher incidence of PLIA than BMS. Also, +PLIA stents had greater neointima than PLIA stents. Histological analysis revealed the existence of fibrinoid and proteoglycans at the site of PLIA.PLIA might be represented by the presence of fibrinoid and proteoglycans, and associated with neointimal proliferation after stenting.

Abstract

The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR).IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P<0.01). However, there was large overlap between IMR in both groups, with 69% of IMR values in patients with atheroma being within the control range. Mean FFR was also higher in the control group (0.96+/-0.02, range 0.93-1.00) than in the atheroma group (0.85+/-0.14, range 0.19-1.00) (P<0.01). There was no correlation between IMR and FFR (r=0.09; P=0.24), even when results in the control (r=0.02; P=0.92) and atheroma (r=0.15; P=0.10) groups were analysed in isolation. Using stepwise multiple regression analysis presence/absence of atheroma (ss=0.42; P=0.02) was the only independent determinant of IMR.Mean IMR is higher in patients with epicardial atherosclerosis. However, there is a large overlap between IMR in patients with and without epicardial atherosclerosis.

Abstract

We sought to investigate the mechanism of geometric changes after main branch (MB) stent implantation and to identify the predictors of functionally significant "jailed" side branch (SB) lesions.Seventy-seven patients with bifurcation lesions were prospectively enrolled from 8 centers. MB intravascular ultrasound was performed before and after MB stent implantation, and fractional flow reserve was measured in the jailed SB. The vessel volume index of both the proximal and distal MB was increased after stent implantation. The plaque volume index decreased in the proximal MB (9.1+/-3.0 to 8.4+/-2.4 mm(3)/mm, P=0.001), implicating plaque shift, but not in the distal MB (5.4+/-1.8 to 5.3+/-1.7 mm(3)/mm, P=0.227), implicating carina shifting to account for the change in vessel size (N=56). The mean SB fractional flow reserve was 0.71+/-0.20 (N=68) and 43% of the lesions were functionally significant. Binary logistic-regression analysis revealed that preintervention % diameter stenosis of the SB (odds ratio=1.05; 95% CI, 1.01 to 1.09) and the MB minimum lumen diameter located distal to the SB ostium (odds ratio=3.86; 95% CI, 1.03 to 14.43) were independent predictors of functionally significant SB jailing. In patients with > or =75% stenosis and Thrombolysis In Myocardial Infarction grade 3 flow in the SB, no difference in post-stent angiographic and intravascular ultrasound parameters was found between SB lesions with and without functional significance.Both plaque shift from the MB and carina shift contribute to the creation/aggravation of an SB ostial lesion after MB stent implantation. Anatomic evaluation does not reliably predict the functional significance of a jailed SB stenosis.

Abstract

To determine the safety and immediate efficacy after balloon aortic valvuloplasty (BAV) with a new, low-profile balloon.BAV has a continuing role in the management of high-risk patients with severe aortic stenosis (AS). BAV with traditional noncompliant balloons requires a large femoral arteriotomy and is associated with high rates of access site complications.We retrospectively reviewed medical records of 20 consecutive patients undergoing BAV for severe AS. Retrograde transfemoral BAV was performed with a low-profile, compliant valvuloplasty balloon. Before and after BAV, transaortic gradients were measured invasively and by echocardiography, and aortic valve area (AVA) calculated. Access site complications, functional class and survival were recorded.Patients were 79 +/- 12 years old and had an estimated mortality from open aortic valve replacement of (12.5 +/- 9.6)%. By catheterization, mean aortic gradient fell from 44 +/- 15 to 29 +/- 10 mm Hg (P < 0.001) and AVA increased from 0.63 +/- 0.22 to 0.89 +/- 0.33 cm(2) (P < 0.001). New York Heart Association functional class improved from 3.5 +/- 0.7 to 2.7 +/- 0.8. Procedural mortality was 0%. There were no vascular complications or significant worsening of aortic regurgitation.Transfemoral BAV using a low-profile compliant balloon is feasible with acceptable immediate results and safety.

Abstract

The aim of this study was to investigate the correlation between myocardial ischemia detected by myocardial perfusion imaging (MPI) with single-photon emission computed tomography with intracoronary pressure-derived fractional flow reserve (FFR) in patients with multivessel coronary disease at angiography.Myocardial perfusion imaging can underestimate the number of ischemic territories in patients with multivessel disease. However, there are limited data comparing MPI and FFR, a highly accurate functional index of myocardial ischemia, in multivessel coronary disease.Sixty-seven patients (201 vascular territories) with angiographic 2- or 3-vessel coronary disease were prospectively scheduled to undergo within 2 weeks MPI (rest/stress adenosine) and FFR in each vessel.In 42% of patients, MPI and FFR detected identical ischemic territories (mean number of territories 0.9 +/- 0.8 for both; p = 1.00). In the remaining 36% MPI underestimated (mean number of territories; MPI: 0.46 +/- 0.6, FFR: 2.0 +/- 0.6; p < 0.001) and in 22% overestimated (mean number of territories; MPI: 1.9 +/- 0.8, FFR: 0.5 +/- 0.8; p < 0.001) the number of ischemic territories in comparison with FFR. There was poor concordance between the ability of the 2 methods to detect myocardial ischemia on both a per-patient (kappa = 0.14 [95% confidence interval: -0.10 to 0.39]) and per-vessel (kappa = 0.28 [95% confidence interval: 0.15 to 0.42]) basis.Myocardial perfusion imaging with single-photon emission computed tomography has poor concordance with FFR and tends to underestimate or overestimate the functional importance of coronary stenosis seen at angiography in comparison with FFR in patients with multivessel disease. These findings might have important consequences in using MPI to determine the optimal revascularization strategy in patients with multivessel coronary disease.

Abstract

To evaluate the safety and patterns of use of targeted renal therapy (TRT) with the Benephit system. TRT, the delivery of therapeutic agents directly to the kidneys by renal arterial infusion, has the advantage of providing a higher local effective dose with potentially greater renal effects, while limiting systemic adverse effects due to renal first-pass elimination.The Benephit System Renal Infusion Therapy (Be-RITe!) Multicenter Registry was a post-market registry following patients treated using the Benephit systems for TRT. The registry enrolled 501 patients (332 men; mean age 72.2+/-9.5 years) at high risk for contrast-induced nephropathy (CIN) during coronary or peripheral angiography/intervention or cardiovascular surgery. The Mehran score was used to compare the actual to predicted incidence of CIN within 48 hours post procedure.Bilateral renal artery cannulation was successful in 94.2%, with a mean cannulation time of 2.0 minutes. Either fenoldopam mesylate, sodium bicarbonate, alprostadil, or B-type natriuretic peptide (BNP) was infused for 184+/-212 minutes. Mean creatinine levels did not change significantly (baseline, 24, and 48 hours post procedure: 1.95, 1.99, and 1.98 mg/dL, respectively; p = NS). In 285 patients who received TRT with fenoldopam and were followed for at least 48 hours, the incidence of CIN was 71% lower than predicted (8.1% actual CIN versus 28.0% predicted; p<0.0001). Only 4 (1.4%) patients required dialysis (versus the 2.6% predicted rate, p = NS).The Benephit system and TRT during coronary and endovascular procedures in patients at high risk for renal failure is simple to use and safe. With the infusion of intrarenal fenoldopam, the incidence of CIN was significantly lower than predicted by risk score calculations.

Abstract

Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation.Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.

Abstract

The purpose of this study was to evaluate optical coherence tomography (OCT) for detecting small degrees of in-stent neointima (ISN) after stent implantation compared with intravascular ultrasound (IVUS).The importance of detecting neointimal coverage of stent struts has grown with the appreciation of the increased risk for late stent thrombosis after drug-eluting stent (DES) implantation. Intravascular ultrasound, the current standard for evaluating the status of DES, lacks the resolution to detect the initial neointimal coverage. Optical coherence tomography has greater resolution but has not yet been compared with IVUS in vivo with histological correlation for validation.Intravascular ultrasound and OCT were performed with motorized pullback imaging in 6 pigs across 33 stents, 1 month after implantation. Each pig was euthanized, and histological measurements of vessel, stent, and lumen dimensions were performed in 3 sections of each stent. A small degree of ISN was defined as occupying <30% of the stent area measured with histology. The IVUS, OCT, and histological assessment of ISN were compared in matched cross-sections of the stents with a small degree of ISN.Eleven stents had a small degree of ISN (average ISN area: 1.26 +/- 0.46 mm(2), and percent area obstruction: 21.4 +/- 5.2%). Compared with histology, the diagnostic accuracy of OCT (area under the receiver operating characteristic curve [AUC] = 0.967, 95% confidence interval [CI] 0.914 to 1.019) was higher than that of IVUS (AUC = 0.781, 95% CI 0.621 to 0.838).Optical coherence tomography detects smaller degrees of ISN more accurately than IVUS and might be a useful method for identifying neointimal coverage of stent struts after DES implantation.

Abstract

Cardiac allograft vasculopathy (CAV) is a major cause of death after heart transplantation (HT). The reduced bioavailability of endothelium-derived nitric oxide may play a role in endothelial vasodilator dysfunction and thus in the structural changes characterizing CAV. A potential contributor to endothelial pathobiology is asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor. It was hypothesized that ADMA concentrations may influence CAV progression during the first postoperative year.Thirty-two consecutive HT recipients underwent intravascular ultrasound evaluation at month 1 and year 1 after HT. Immunosuppression included mycophenolate mofetil (MMF, n=16) and sirolimus (n=16). Change in intimal volume greater than the median and vascular remodeling were major outcome measures.Plasma ADMA levels were associated with subsequent development of intimal hyperplasia (risk ratio [95% confidence interval] =2.72 [1.06-6.94]; P=0.038), and plasma ADMA levels greater than 0.70 micromol/L most accurately identified patients who would have developed intimal hyperplasia. However, ADMA levels did not correlate with negative coronary remodeling. Treatment with sirolimus, as compared with MMF, was associated with significantly lower ADMA levels (0.65+/-0.12 vs. 0.77+/-0.10 micromol/L; P<0.01) and less intimal hyperplasia (risk ratio [95% confidence interval] = 0.08 [0.01-0.56]; P=0.01).Elevated plasma ADMA is associated with coronary intimal hyperplasia, supporting the importance of nitric oxide synthase inhibition in CAV pathogenesis. Treatment with sirolimus (rather than MMF) is associated with lower ADMA levels and reduced risk of accelerated CAV.

Abstract

We previously reported that negative remodeling, not plaque progression, correlated with lumen loss during the first year after cardiac transplantation and that cytomegalovirus antibody seropositivity correlated with increased negative remodeling and greater lumen loss. Whether these findings persist between years 1 and 2 after transplantation is unknown.Serial 3-dimensional intravascular ultrasound analysis in the left anterior descending coronary artery was performed in 30 cardiac transplant recipients at year 1 and 2 after transplantation. Vessel, lumen, and plaque area were determined at 0.5-mm axial intervals in the first 50 mm of the left anterior descending coronary artery, and volumes were computed using Simpson's method. Univariate and multivariate regression analyses were performed to identify clinical predictors of change in coronary dimensions.Although mean vessel area did not change (13.6+/-3.4 to 13.4+/-3.3 mm/mm(3), P=0.45), mean plaque area increased (3.4+/-2.3 to 3.8+/-2.2 mm/mm(3), P=0.012), resulting in significant mean lumen area loss (10.3+/-2.5 to 9.6+/-2.3 mm/mm(3), P=0.016). However, the degree of luminal change strongly correlated with the degree of change in vessel size (R=0.81, P<0.0001), but not with change in plaque amount (R=-0.19, P=0.32). In fact, in 57% of the patients who demonstrated lumen loss, negative remodeling contributed more to lumen loss than did plaque progression. Diabetes at 2 years was the only significant independent clinical predictor of plaque progression and lumen loss.Despite significant plaque progression, negative remodeling correlated with coronary lumen loss between years 1 and 2 after cardiac transplantation.

Abstract

Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.

Abstract

We sought to evaluate the prognostic significance of premature ventricular contractions (PVCs) on a routine electrocardiogram (ECG) and to evaluate the relationship between heart rate and PVCs.Computerized 12-lead ECGs of 45,402 veterans were analyzed. Vital status was available through the California Health Department Service.There were 1731 patients with PVCs (3.8%). Compared to patients without PVCs, those with PVCs had significantly higher all-cause (39% vs 22%, P < 0.001) and cardiovascular mortality (20% vs 8%, P < 0.001). PVCs remain a significant predictor even after adjustment for age and other ECG abnormalities. The presence of multiple PVCs or complex morphologies did not add significant additional prognostic information. Those patients with PVCs had a significantly higher heart rate than those without PVCs (mean +/- SD: 78.6 +/- 15 vs 73.5 +/- 16 bpm, P < 0.001). When patients were divided into groups by heart rate (<60, 60-79, 80-99 and >100 bpm) and by the presence or absence of PVCs, mortality increased progressively with heart rate and doubled with the presence of PVCs. Using regression analysis, heart rate was demonstrated to be an independent and significant predictor of PVCs.PVCs on a resting ECG are a significant and independent predictor of all-cause and cardiovascular mortality. Increased heart rate predicts mortality in patients with and without PVCs and the combination dramatically increases mortality. These findings together with the demonstrated independent association of heart rate with PVCs suggest that a hyperadrenergic state is present in patients with PVCs and that it likely contributes to their adverse prognosis.

Abstract

Metabolic and immuno-inflammatory risk factors contribute to cardiac allograft vasculopathy (CAV) pathogenesis. Although systemic inflammation, as detected by C-reactive protein (CRP), predicts CAV development, the relationship between CRP and markers of metabolic abnormalities remains unexplored.CRP and the entire metabolic panel were evaluated in 98 consecutive heart transplant recipients at the time of annual coronary angiography, 5.8 years after transplant (range, 1-12 years). A ratio of triglycerides (TG) to high-density lipoproteins (HDL) of 3.0 or more was considered a marker of insulin resistance. CAV prevalence was defined by angiography, and subsequent prognosis was evaluated as incidence of major cardiac adverse events.CRP was higher in the 34 patients with angiographic CAV than in those without CAV (1.10 +/- 0.20 vs 0.50 +/- 0.05 mg/dl, p < 0.001). Patients with insulin resistance had higher CRP concentrations (p = 0.023) and higher CAV prevalence (p = 0.005). High CRP and a TG/HDL of 3.0 or more were independently associated with an increased likelihood of CAV (odds ratio, > or = 3.9; p = 0.02) and predicted an increased risk of major cardiac adverse events. The combination of high CRP and a TG/HDL of 3.0 or more identified a subgroup of patients having a 4-fold increased risk for CAV and a 3-fold increased risk for major cardiac adverse events compared with patients with low CRP and normal values for metabolic indicators.Both CRP and insulin resistance, as estimated by TG/HDL, appear to be strong, synergic risk factors for CAV and for major cardiac adverse events. These findings support the hypothesis that in heart transplant recipients, systemic inflammation may be an important mediator of graft vascular injury associated with metabolic syndrome.

Abstract

Significant changes in coronary artery structure, including intimal thickening and vessel remodeling, occur early after cardiac transplantation. The degree to which these changes compromise coronary lumen dimensions, and the clinical factors that affect these changes, remain controversial.Thirty-eight adult cardiac transplant recipients underwent coronary angiography and volumetric intravascular ultrasound (IVUS) evaluation of the left anterior descending artery within 8 weeks of transplantation and at 1 year. Clinical parameters including donor and recipient characteristics, rejection episodes, and serology were prospectively recorded. Two-dimensional IVUS measurements and vessel, lumen and plaque volume were calculated at both time points and compared. Multivariate regression analysis was performed to reveal clinical predictors of change in coronary dimensions.During the first year after transplantation, significant decreases in vessel size (negative remodeling) and lumen size were observed with significant increases in plaque burden based on IVUS analyses. Loss of lumen volume correlated significantly with the degree of negative remodeling (R=0.82, P<0.0001), but not with changes in plaque burden (R=0.08, P=0.64). Patients with the greatest increase in plaque volume had significantly less negative remodeling (R=0.53, P=0.0006). Transplant recipient cytomegalovirus (CMV) antibody seropositivity and lack of aggressive prophylaxis against CMV infection/reactivation were significant independent predictors of greater negative remodeling (P<0.01 and P=0.03, respectively) and greater lumen loss (P=0.02 and P=0.03, respectively).Negative remodeling is primarily responsible for coronary artery lumen loss during the first year after cardiac transplantation. CMV seropositivity and lack of aggressive CMV prophylaxis correlate with increased negative remodeling, resulting in greater lumen loss.

Abstract

Asymptomatic cytomegalovirus (CMV) replication is frequent after cardiac transplantation in recipients with pretransplantation CMV infection. How subclinical viral replication influences cardiac allograft disease remains poorly understood, as does the importance of T-cell immunity in controlling such replication.Thirty-nine cardiac recipients who were pretransplantation CMV antibody positive were longitudinally studied for circulating CMV-specific CD4 and CD8 T-cell responses, CMV viral load in blood neutrophils, and allograft rejection during the first posttransplantation year. Nineteen of these recipients were also analyzed for changes of coronary artery intimal, lumen, and whole-vessel area. All recipients received early prophylactic therapy with ganciclovir. No recipients developed overt CMV disease. Those with detectable levels of CMV-specific CD4 T cells in the first month after transplantation were significantly protected from high mean and peak posttransplantation viral load (P<0.05), acute rejection (P<0.005), and loss of allograft coronary artery lumen (P<0.05) and of whole-vessel area (P<0.05) compared with those who lacked this immune response. The losses of lumen and vessel area were both significantly correlated with the time after transplantation at which a CD4 T-cell response was first detected (P<0.05) and with the cumulative graft rejection score (P<0.05).The early control of subclinical CMV replication after transplantation by T-cell immunity may limit cardiac allograft rejection and vascular disease. Interventions to increase T-cell immunity might be clinically useful in limiting these adverse viral effects.

Abstract

With advances in technology, the physiological assessment of coronary artery disease in patients in the catheterization laboratory has become increasingly important in both clinical and research applications, but this assessment has evolved without standard nomenclature or techniques of data acquisition and measurement. Some questions regarding the interpretation, application, and outcome related to the results also remain unanswered. Accordingly, this consensus statement was designed to provide the background and evidence about physiological measurements and to describe standard methods for data acquisition and interpretation. The most common uses and support data from numerous clinical studies for the physiological assessment of coronary artery disease in the cardiac catheterization laboratory are reviewed. The goal of this statement is to provide a logical approach to the use of coronary physiological measurements in the catheterization lab to assist both clinicians and investigators in improving patient care.

Abstract

Contrast-induced nephropathy (CIN) remains an important complication of angiographic procedures, particularly among patients with significant renal impairment. To date, vasodilator therapies such as fenoldopam have failed to prevent CIN, possibly because significant hypotension as a result of systemic infusion has limited the ability to deliver adequate drug levels to the renal vasculature. We present a case of averted CIN after multivessel coronary intervention in a diabetic patient with severe renal insufficiency, potentially due to bilateral renal arterial infusion of fenoldopam. Our subsequent experience with intrarenal fenoldopam in nine additional procedures in eight other high risk patients resulted in one case of asymptomatic transient CIN. Further studies are warranted to evaluate the efficacy of intrarenal administration of vasodilator therapies such as fenoldopam for the prevention of CIN.

Abstract

We sought to determine the incidence, clinical features, and risk factors for retroperitoneal hematoma (RPH) after percutaneous coronary intervention (PCI).Little is known about the clinical features, outcomes, and determinants of this serious complication in the contemporary era of PCI.A retrospective analysis yielded 26 cases of RPH out of 3,508 consecutive patients undergoing PCI between January 2000 and January 2004. Cases were compared with a randomly selected sample of 50 control subjects without RPH.The incidence of RPH was 0.74%. Features of RPH included abdominal pain (42%), groin pain (46%), back pain (23%), diaphoresis (58%), bradycardia (31%), and hypotension (92%). The mean systolic blood pressure nadir was 75 mm Hg. The hematocrit dropped by 11.5 +/- 5.1 points from baseline in RPH patients, as compared with 2.3 +/- 3.3 points in controls (p < 0.0001). The mean hospital stay was longer in RPH patients (2.9 +/- 3.8 days vs. 1.7 +/- 1.5 days, p = 0.06). The following variables were found to be independent predictors of RPH: female gender (odds ratio [OR] 5.4, p = 0.005), low body surface area (BSA <1.73 m(2); OR 7.1, p = 0.008), and higher femoral artery puncture (OR 5.3, p = 0.013). There was no association between RPH and arterial sheath size, use of glycoprotein IIb/IIIa inhibitors, or deployment of a vascular closure device.Female gender, low BSA, and higher femoral artery puncture are significant risk factors for RPH. Awareness of the determinants and clinical features of RPH may aid in prevention, early recognition, and prompt treatment.

Abstract

An emotionally-distressed, elderly Caucasian woman presented with chest pain and hypertension. Electrocardiogram showed inferior ST-segment elevation, and an urgent cardiac catheterization was performed. Coronary angiography revealed normal appearing coronary arteries; however, left ventriculography showed extensive left ventricular apical akinesis. The patient had a mild rise in cardiac enzyme levels indicative of myocardial injury. She was discharged after an uncomplicated in-hospital course. One month later, the left ventricular wall motion abnormality had improved. In this report, the authors discuss this compilation of findings known as tako-tsubo-like left ventricular dysfunction.

Abstract

Whether minimal microvascular resistance of the myocardium is affected by the presence of an epicardial stenosis is controversial. Recently, an index of microcirculatory resistance (IMR) was developed that is based on combined measurements of distal coronary pressure and thermodilution-derived mean transit time. In normal coronary arteries, IMR correlates well with true microvascular resistance. However, to be applicable in the case of an epicardial stenosis, IMR should account for collateral flow. We investigated the feasibility of determining IMR in humans and tested the hypothesis that microvascular resistance is independent of epicardial stenosis.Thirty patients scheduled for percutaneous coronary intervention were studied. The stenosis was stented with a pressure guidewire, and coronary wedge pressure (P(w)) was measured during balloon occlusion. After successful stenting, a short compliant balloon with a diameter 1.0 mm smaller than the stent was placed in the stented segment and inflated with increasing pressures, creating a 10%, 50%, and 75% area stenosis. At each of the 3 degrees of stenosis, fractional flow reserve (FFR) and IMR were measured at steady-state maximum hyperemia induced by intravenous adenosine. A total of 90 measurements were performed in 30 patients. When uncorrected for P(w), an apparent increase in microvascular resistance was observed with increasing stenosis severity (IMR=24, 27, and 37 U for the 3 different degrees of stenosis; P<0.001). In contrast, when P(w) is appropriately accounted for, microvascular resistance did not change with stenosis severity (IMR=22, 23, and 23 U, respectively; P=0.28).Minimal microvascular resistance does not change with epicardial stenosis severity, and IMR is a specific index of microvascular resistance when collateral flow is properly taken into account.

Abstract

With increasing research on vulnerable plaques and uncertainty regarding which lesions require revascularization, the goal of this review is to clarify the indications for percutaneous coronary intervention and discuss which lesions do not warrant treatment by intervention. This paper also briefly reviews the potential advantages and limitations of technology that may enable detection of atherosclerotic plaques that are prone to rupture and discusses the future utility of these technologies in prevention of acute coronary syndromes. Providing an evidence-based understanding of lesion morphology and clinical variables that influence outcome enables the interventional cardiologist to determine which atherosclerotic plaques require PCI.

Abstract

Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.

Abstract

Thermodilution coronary flow reserve (CFRthermo) is a new technique for invasively measuring coronary flow reserve (CFR) with a coronary pressure wire and is based on the ability of the pressure transducer to also measure temperature changes. Whether CFRthermo correlates well enough with absolute flow-derived CFR (CFRflow) to replace Doppler wire-derived CFR (CFRDoppler) remains unclear.In an open-chest pig model, CFRthermo was measured in the left anterior descending (LAD) artery and compared with CFRDoppler and CFRflow, measured with an external flow probe placed around the LAD. In 9 pigs, CFR was measured simultaneously by all 3 means in the normal LAD and after creation of an epicardial LAD stenosis. To determine the added effect of microvascular disease, measurements of flow reserve were also performed after disruption of the coronary microcirculation with embolized microspheres. Intracoronary papaverine (20 mg) was used to induce hyperemia. In a total of 61 paired measurements, CFRthermo correlated strongly with the reference standard CFRflow (r=0.85, P<0.001). CFRDoppler correlated less well with CFRflow (r=0.72, P<0.001). Bland-Altman analysis showed a closer agreement between CFRthermo and CFRflow.CFRthermo correlates better with CFRflow than does CFRDoppler.

Abstract

The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy.In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was < or =0.80, the upper boundary of the gray zone of the ischemic threshold. There was a significant inverse correlation between FFR and IVUS-derived measures of plaque burden, including percent plaque volume (r=0.55, P<0.0001). The average CFRthermo was 2.5+/-1.2; in 47% of cases, CFRthermo was < or =2.0. In 14%, the FFR was normal (> or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction.FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.

Abstract

Most patients come to the catheterization laboratory without prior functional tests, which makes the cost-effective treatment of patients with intermediate coronary lesions a practical challenge.We developed a decision model to compare the long-term costs and benefits of 3 strategies for treating patients with an intermediate coronary lesion and no prior functional study: 1) deferring the decision for percutaneous coronary intervention (PCI) to obtain a nuclear stress imaging study (NUC strategy); 2) measuring fractional flow reserve (FFR) at the time of angiography to help guide the decision for PCI (FFR strategy); and 3) stenting all intermediate lesions (STENT strategy). On the basis of the literature, we estimated that 40% of intermediate lesions would produce ischemia, 70% of patients treated with PCI and 30% of patients treated medically would be free of angina after 4 years, and the quality-of-life adjustment for living with angina was 0.9 (1.0 = perfect health). We estimated the cost of FFR to be 761 dollars, the cost of nuclear stress imaging to be 1093 dollars, and the cost of medical treatment for angina to be 1775 dollars per year. The extra cost of splitting the angiogram and PCI as dictated by the NUC strategy was 3886 dollars by use of hospital cost-accounting data. Sensitivity and threshold analyses were performed to determine which variables affected our results.The FFR strategy saved 1795 dollars per patient compared with the NUC strategy and 3830 dollars compared with the STENT strategy. Quality-adjusted life expectancy was similar among the 3 strategies (NUC-FFR = 0.8 quality-adjusted days, FFR-STENT = 6 quality-adjusted life days). Compared with the FFR strategy, the NUC strategy was expensive (>800,000 dollars per quality-adjusted life year gained). Both screening strategies were superior to (less cost, better outcomes) the STENT strategy. Sensitivity analysis indicated that the NUC strategy would only become attractive (<50,000 dollars/quality-adjusted life years compared with FFR) if the specificity of nuclear stress imaging was >25% better than FFR. Our results were not altered significantly by changing the other assumptions.In patients with an intermediate coronary lesion and no prior functional study, measuring FFR to guide the decision to perform PCI may lead to significant cost savings compared with performing nuclear stress imaging or with simply stenting lesions in all patients.

Abstract

Previous work has suggested that platelet glycoprotein IIb/IIIa receptor blockade may confer benefit in the treatment of acute myocardial infarction. The TIGER-PA pilot trial was a single-center randomized study to evaluate the safety, feasibility, and utility of early tirofiban administration before planned primary angioplasty in patients presenting with acute myocardial infarction.A total of 100 patients presenting with acute myocardial infarction were randomized to either early administration of tirofiban in the emergency room or later administration in the catheterization laboratory. The primary outcome measures were initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion ("blush"). Thirty-day major adverse cardiac events were also assessed. Angiographic outcomes demonstrate a significant improvement in initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion when patients are given tirofiban in the emergency room before primary angioplasty. The rate of 30-day major adverse cardiac events suggests that early administration may be beneficial.This pilot study suggests that early administration of tirofiban improves angiographic outcomes and is safe and feasible in patients undergoing primary angioplasty for acute myocardial infarction.

Abstract

Angiography is notoriously poor at distinguishing ischemia-producing from non-ischemia-producing intermediate coronary lesions. Here, three invasive modalities for evaluating the physiologic significance of moderate coronary stenoses are reviewed: Doppler wire-derived measurement of coronary flow reserve (CFR), coronary pressure wire-derived fractional flow reserve (FFR), and intravascular ultrasound (IVUS) imaging. Studies investigating the correlation between each of these modalities and various noninvasive tests (eg, nuclear perfusion imaging or stress echocardiography) are discussed. Each of these invasive modalities has its limitations: CFR is limited by its dependence on heart rate and blood pressure, calling into question its reproducibility; both FFR and CFR are limited by their reliance upon achieving maximal hyperemia; and IVUS is limited by the fact that it provides anatomic information only. Ultimately, FFR appears to be the ideal method for interrogating intermediate coronary lesions.

Abstract

Coronary stenting is associated with a restenosis rate of 15% to 20% at 6-month follow-up, despite optimum angiographic stent implantation. In this multicenter registry, we investigated the relation between optimum physiological stent implantation as assessed by poststent fractional flow reserve (FFR) and outcome at 6 months.In 750 patients, coronary pressure measurement at maximum hyperemia was performed after angiographically apparently satisfactory stent implantation. Poststenting FFR was calculated and related to major adverse events (including need for repeat target vessel revascularization) at 6 months. In 76 patients (10.2%), at least 1 adverse event occurred. Five patients died, 19 experienced myocardial infarction, and 52 underwent at least 1 repeat target vessel revascularization. By multivariate analysis, FFR immediately after stenting was the most significant independent variable related to all types of events. In 36% of the patients, FFR normalized (>0.95), and event rate was 4.9% in that group. In 32% of the patients, poststent FFR was between 0.90 and 0.95, and event rate was 6.2%. In 32% of patients, poststent FFR was <0.90, and event rate was 20.3%. In 6% of the patients, FFR was <0.80, and event rate was 29.5% (P<0.001).FFR after stenting is a strong independent predictor of outcome at 6 months.

Abstract

Recently, several treadmill scores have been proposed as means for improving the diagnostic accuracy of the exercise treadmill test (ETT). Questions remain regarding the diagnostic accuracy of treadmill scores when applied to a different patient population than that from which they were derived; furthermore, many treadmill scores have not been compared with one another in the same population.The diagnostic accuracy of treadmill scores may not be the same.A retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. All patients underwent a standard ETT followed by coronary angiography. Using angiographic evidence of coronary artery disease (CAD) as a reference, the area under the curve (AUC) of receiver operator characteristic (ROC) plots of the ST response alone, the Duke Treadmill Score (DTS), the Morise score, the Detrano score, the VA score, and a Consensus score consisting of the Morise, Detrano, and VA scores together were calculated and compared. The predictive accuracies of the DTS and the Consensus score to stratify patients for the likelihood of CAD were calculated and compared.In all, 1,282 patients without a prior myocardial infarction had an ETT and coronary angiography. The AUC (+/- standard error) was 0.67+/-0.01 for the ST response, 0.73+/-0.01 for DTS, 0.76+/-0.01 for Detrano score, 0.77+/-0.01 for Morise score, 0.78+/-0.01 for VA score, and 0.78+/-0.01 for Consensus score. The AUC for each treadmill score was significantly higher (z-score > 1.96) than for the ST response alone. The AUC of DTS was significantly lower than all other treadmill scores (z-score > 1.96). The predictive accuracy (+/-95% confidence interval) of the DTS to risk stratify patients into high and low likelihood for CAD was 71 (65-77)%, versus 80 (74-86)% for the Consensus score (p < 0.0001).In this population, the DTS remains useful for diagnosing CAD and stratifying for the likelihood of CAD, although it is less accurate than other treadmill scores.

Abstract

Determination of fractional flow reserve (FFR) has been proposed as a means to assess stent deployment. In this prospective, multicenter trial, we evaluate the use of FFR to optimize stenting by comparing it with standard intravascular ultrasound (IVUS) criteria.Eighty-four stable patients with isolated coronary lesions underwent coronary stent deployment starting at 10 atm and increased serially by 2 atm until the FFR was >/=0.94 or 16 atm was achieved. IVUS was then performed. FFR was measured with a coronary pressure wire with intracoronary adenosine to induce hyperemia. The diagnostic characteristics of an FFR <0.94 to predict suboptimal stent expansion by IVUS, defined in both absolute and relative terms, were calculated. Over a range of IVUS criteria, the highest sensitivity, specificity, and predictive accuracy of FFR were 80%, 30%, and 42%, respectively. Receiver operator characteristic analysis defined an optimal FFR cut point at >/=0.96; at this threshold, the sensitivity, specificity, and predictive accuracy of FFR were 75%, 58%, and 62%, respectively (P=0.03 for comparison of predictive accuracy, P=0.01 for concordance between FFR and IVUS). The negative predictive value was 88%. Significantly better diagnostic performance was achieved in a subgroup that received higher doses (>30 microgram) of intracoronary adenosine during pressure measurements, suggesting that FFR might be overestimated in the other group.A fractional flow reserve <0.96, measured after stent deployment, predicts a suboptimal result based on validated intravascular ultrasound criteria; however, an FFR >/=0.96 does not reliably predict an optimal stent result. Higher doses of intracoronary adenosine than previously used to measure FFR improve these results.

Abstract

Our purpose was to assess the diagnostic characteristics of the exercise test in patients who fail to reach conventional target heart rates and in patients on beta-blockers.Exercise test results are often considered "inadequate" or "nondiagnostic" in patients taking beta-blockers and in patients who do not achieve 85% of their age-predicted maximal heart rate.The results of exercise tests and coronary angiography performed to evaluate chest pain in 1282 male patients without a prior history of myocardial infarction, coronary revascularization, diagnostic Q wave on the baseline electrocardiogram, or previous cardiac catheterization were analyzed with respect to beta-blocker exposure and failure to reach 85% age-predicted maximal heart rate. Sensitivity, specificity, and predictive accuracy of exercise testing, as well as area under the curve for the receiver operating characteristic plots were calculated for these subgroups with use of coronary angiography as the reference. The angiographic criterion for significant coronary artery disease was 50% narrowing or greater in one or more major coronary arteries.The population was divided into 4 exclusive groups on the basis of whether they reached their target heart rates and whether they were receiving beta-blockers. Sixty to 40 percent of this clinical population failed to reach target heart rate, of which 24% (n = 303) were receiving beta-blockers and 40% (n = 518) were not. The group of patients who reached target heart rate and were not taking beta-blockers was taken as the reference group (n = 409). The group of patients supposedly beta-blocked but who reached the target heart rate (n = 52) had hemodynamic and test characteristics similar to those of the reference group and most likely were not taking their beta-blockers or were not adequately dosed. The prevalence of angiographic coronary disease was significantly higher in the 2 groups failing to reach target heart rate, both in the presence and absence of beta-blockers, compared with the reference group (68% and 64%, respectively, vs 49%, P

Abstract

The purpose of this study was to determine the characteristics of exercise treadmill testing in diabetic patients presenting with chest pain.The diagnosis of coronary artery disease (CAD) in diabetic patients is confounded by different manifestations of coronary disease than are seen in the general population. Because of the association of diabetes with accelerated CAD, it is critical to assess the diagnostic utility of the standard exercise test in diabetic patients with chest pain.This study was a retrospective analysis of standard exercise test results in 1,282 male patients without prior myocardial infarction who had undergone coronary angiography and were being evaluated for possible CAD at two Veterans' Administration institutions.In patients with diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 69%; the sensitivity of the exercise test was 47% (95% confidence interval [CI], 41 to 58), and specificity was 81% (95% CI, 68 to 89). In patients without diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 58%; the sensitivity of the exercise test was 52% (95% CI, 48 to 56), and specificity was 80% (95% CI, 76 to 83). The receiver operating characteristic curves were also similar in both diabetic and nondiabetic patients (0.67 and 0.68, respectively).These data demonstrate that the standard exercise test has similar diagnostic characteristics in diabetic as in nondiabetic patients.

Abstract

The goal of the present study was to compare the use of pressure-derived myocardial fractional flow reserve for detecting ischemia with nuclear stress imaging in patients undergoing stent placement for intermediate coronary lesions. We demonstrated that myocardial fractional flow reserve detects ischemia in intermediate coronary lesions accurately when compared with nuclear stress imaging.

The effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill testJOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGYFearon, W. F., Lee, D. P., Froelicher, V. F.2000; 35 (5): 1206-1211

Abstract

The aim of this study is to demonstrate the effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test.Previous studies evaluating the effect of resting ST segment depression on the diagnostic characteristics of exercise treadmill test have been conducted on relatively small patient groups and based only on visual electrocardiogram (ECG) analysis.A retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. One thousand two hundred eighty-two patients without a prior myocardial infarction underwent standard exercise treadmill tests followed by coronary angiography, with coronary artery disease defined as a 50% narrowing in at least one major epicardial coronary artery. Sensitivity, specificity, predictive accuracy and area under the curve of the receiver operating characteristic (ROC) plots were calculated for patients with and without resting ST segment depression as determined by visual or computerized analysis of the baseline ECG.Sensitivity of the exercise treadmill test increased in 206 patients with resting ST segment depression determined by visual ECG analysis compared with patients without resting ST segment depression (77 +/- 7% vs. 45 +/- 4%) and specificity decreased (48 +/- 12% vs. 84 +/- 3%). With computerized analysis, sensitivity of the treadmill test increased in 349 patients with resting ST segment depression compared with patients without resting ST segment depression (71 +/- 6% vs. 42 +/- 4%) and specificity decreased (52 +/- 9% vs. 87 +/- 3%) (p < 0.0001 for all comparisons). There was no significant difference in the area under the curve of the ROC plots (0.66-0.69) or the predictive accuracy (62-68%) between the four subgroups.The diagnostic accuracy and high sensitivity of the exercise treadmill test in a large cohort of patients with resting ST segment depression and no prior myocardial infarction support the initial use of the test for diagnosis of coronary artery disease. The classification of resting ST segment depression by method of analysis (visual vs. computerized) did not affect the results.

Abstract

To help guide physicians in their evaluation of patients with acute coronary syndromes, we investigated whether elevated cardiac troponin I in patients presenting with unstable angina predicts ischemia on stress testing. Elevated cardiac troponin I in patients who present with chest pain and normal creatine kinase levels is associated with ischemia on stress testing, as well as with future cardiac events.

Abstract

A young woman was diagnosed with systemic lupus erythematosus at the age of 7 years and incurred an acute myocardial infarction at the age of 17 years. Her risk factors for coronary artery disease include hypertension, hypercholesterolemia, a relatively long disease duration, a fairly active disease as evidenced by the history of nephrotic syndrome and other organ system involvement, and a long history of prednisone use. It is difficult to determine the etiology of this patient's acute myocardial infarction without coronary artery histopathology, but aspects of her presentation (a history of virulent systemic lupus erythematosus, and the angiographic findings of ectasia and aneurysm) suggest that coronary arteritis was the etiology of her accelerated coronary artery disease and subsequent myocardial infarction. Acute myocardial infarction is an uncommon occurrence in premenopausal women less than 30 years old.35 These patients are typically found to have an associated systemic disease such as diabetes mellitus or familial hypercholesterolemia. Systemic lupus erythematosus is a less common systemic disease associated with premature coronary artery disease. Mechanisms of acute coronary syndromes in these patients include accelerated atherosclerosis, active coronary vasculitis, and/or vasospasm with superimposed thrombosis.